MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Clinical and Experimental Metastasis' source. Wed, 08 Feb 2012 08:41:25 +0100 http://www.medworm.com/index.php?rid=5647043&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj32207530078n874%2F Abstract  c-Met tyrosine kinase hyperactivation is strongly associated with tumor metastasis. In a prior study we showed that BMS-777607, a novel selective small molecule Met kinase inhibitor, potently suppressed ligand-mediated functions in prostate cancer cells. Herein we evaluated the impact of this agent on the potential of the highly metastatic murine KHT sarcoma that carries constitutive activated c-Met. MET gene knockdown was found to reduce spontaneous cell scatter and motility, suggesting a c-Met-dependent disseminating ability in KHT cells. Furthermore, BMS-777607 treatment potently inhibited KHT cell scatter, motility and invasion at doses in the nanomolar range. In contrast, cell proliferation and clonogenicity were modestly affected by BMS-777607. At the molecul... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5647043 Fri, 27 Jan 2012 17:56:43 +0100 5647043 http://www.medworm.com/index.php?rid=5638084&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1714l148q0g31277%2F Abstract  As malignant breast cancers progress, they acquire the ability to spread to other regions of the body, including bone and lung, but the molecular mechanism underlying the increase in metastatic potential is not fully understood. Here we studied murine 4T1E/M3 highly bone marrow metastatic breast cancer cells, which we established previously. These cells show upregulated expression of bone morphogenetic protein (BMP) 7 and BMP receptors, as well as augmented phosphorylation of Smad1/5/8. Both anchorage-independent cell growth measured in colony forming assays and cell migration measured in wound healing assays were suppressed in 4T1E/M3 cells following treatment with a neutralizing anti-BMP7 antibody or knockdown of BMP7 gene expression. In addition, metastasis of ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5638084 Tue, 24 Jan 2012 12:27:28 +0100 5638084 http://www.medworm.com/index.php?rid=5638083&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F96402ml763616053%2F We report here that downregulation of PTPL1 by small interfering RNA in PC3 cells decreases cell proliferation and concomitantly reduces the expression of cell cycle-related proteins such as cyclins E and B1, PCNA, PTTG1 and phospho-histone H3. PTPL1 downregulation also increases the invasion ability of PC3 cells through Matrigel coated membranes. cDNA array of PTPL1-silenced PC3 cells versus control cells showed an upregulation of invasion-related genes such as uPA, uPAR, tPA, PAI-1, integrin α6 and osteopontin. This increased expression was also confirmed in PTPL1-silenced DU145 prostate cancer cells by quantitative real time PCR and western blot. These findings suggest that PTPL1 is an important mediator of central cellular processes such as proliferation and invasion. Conte... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5638083 Tue, 24 Jan 2012 12:27:28 +0100 5638083 http://www.medworm.com/index.php?rid=5638085&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F64l253440586p112%2F This study has important connotations for a role of SPCs in local recurrence. Content Type Journal ArticleCategory Research PaperPages 1-20DOI 10.1007/s10585-011-9450-4Authors Vanisri Raviraj, Australian Centre for Microscopy and Microanalysis (ACMM), AMMRF, The University of Sydney, Madsen Building F09, Room 243, Sydney, NSW 2006, AustraliaHui Zhang, Australian Centre for Microscopy and Microanalysis (ACMM), AMMRF, The University of Sydney, Madsen Building F09, Room 243, Sydney, NSW 2006, AustraliaHsin-ya Chien, Australian Centre for Microscopy and Microanalysis (ACMM), AMMRF, The University of Sydney, Madsen Building F09, Room 243, Sydney, NSW 2006, AustraliaLouise Cole, Advanced Microscopy Facility, Bosch Institute, The University of Sydney, Sydney, NSW 2006, AustraliaErik W. Th... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5638085 Tue, 24 Jan 2012 06:54:48 +0100 5638085 http://www.medworm.com/index.php?rid=5619689&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp21160x14r71572p%2F Abstract  High grade serous ovarian tumors often metastasize transperitoneally, a process that begins when small tumor nodules de-adhere and are released into the fluid of the abdominal cavity where they float freely to reach new sites on the peritoneal wall. Podocalyxin, a small anti-adhesive sialomucin, has been shown to contribute to non-adhesive membrane domain formation in some epithelia and is overexpressed in a variety of cancers. We therefore assessed podocalyxin expression on a previously characterized tissue microarray and found that 87% (169/194) of high grade serous epithelial ovarian carcinomas were positive for podocalyxin. In addition, cell surface localization of podocalyxin was associated with a significant decrease in disease-free survival in these tumors.... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5619689 Fri, 20 Jan 2012 07:04:39 +0100 5619689 http://www.medworm.com/index.php?rid=5619688&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyr21581225775326%2F Abstract  Xenograft models of human diffuse large B cell lymphoma (DLBCL) are widely used to test new drugs against this neoplasia. Most of them, however, are subcutaneous xenografts that do not show a disseminated disease as it is found in the human neoplasia. In this paper, we aimed to develop a disseminated xenograft model of DLBCL by performing a subcutaneous passage of DLBCL cells before their intravenous injection in mice. WSU-DLCL-2 (WSU) cells were injected into both flanks of NOD/SCID mice. The subcutaneous tumours were disaggregated and a cell suspension (WSU-SC) was obtained. Two groups of 10 NOD/SCID mice were intravenously injected with WSU-SC or WSU cells. All mice injected with WSU-SC cells developed lymphoma in 32–47 days and showed lymph node and bon... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5619688 Fri, 20 Jan 2012 07:04:39 +0100 5619688 http://www.medworm.com/index.php?rid=5619690&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd58577r422k65402%2F In conclusion, these results may contribute to the JunB-associated malignant phenotype of gastric cancers by regulating MMP-9, and serve as a novel therapeutic target for stomach cancer therapy in the future. Content Type Journal ArticleCategory Research PaperPages 1-10DOI 10.1007/s10585-011-9449-xAuthors Kyung Hee Lee, Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Republic of KoreaJae-Ryong Kim, Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong, Daegu, 705-717 Republic of Korea Journal Clinical and Experimental MetastasisOnline ISSN 1573-7276Print ISSN 0262-0898 (Source: Clinical and Experimental Metastasis) Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5619690 Wed, 18 Jan 2012 06:48:28 +0100 5619690 http://www.medworm.com/index.php?rid=5619691&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F56740x2117305t57%2F Abstract  Epithelial ovarian cancer (EOC) cells have the ability to form multi-cellular aggregates in malignant ascites which dramatically alters cell signalling, survival, and metastatic potential. Herein, we demonstrate that patient ascites-derived EOC cells down-regulate endogenous bone morphogenetic protein (BMP) signalling by decreasing BMP ligand expression when grown in suspension culture to form spheroids. Enforced BMP signalling in these cells via constitutively-active BMP type I ALK3QD receptor expression causes the formation of smaller, more loosely-aggregated spheroids. Additionally, ALK3QD-expressing spheroids have an increased rate of adhesion and dispersion upon reattachment to substratum. Inhibition of endogenous BMP signalling using recombinant Noggin or smal... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5619691 Tue, 17 Jan 2012 07:13:02 +0100 5619691 http://www.medworm.com/index.php?rid=5596959&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhx80k463575lr731%2F Abstract  Morbidity and mortality of breast cancer patients are drastically increased when primary tumor cells are able to spread to distant sites and proliferate to become secondary lesions. Effective treatment of metastatic disease has been limited; therefore, an increased molecular understanding to identify biomarkers and therapeutic targets is needed. Breast cancer metastasis suppressor 1 (BRMS1) suppresses development of pulmonary metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Little is known of Brms1 function throughout the initiation and progression of mammary carcinoma. The goal of this study was to investigate mechanisms of Brms1-mediated metastasis suppression in transgenic mice that express Brms1 using polyoma middl... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5596959 Thu, 12 Jan 2012 16:49:15 +0100 5596959 http://www.medworm.com/index.php?rid=5581002&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj7051207708u5864%2F Abstract  Increased expression of CD133 (Prominin-1), an important cancer stem cell-associated marker, has been observed in the cancer stem cells of a variety of human and mouse cancers. However, no natural ligand of CD133 has yet been identified and little is known about its function. In the present study, LS-7 (amino acid sequence: LQNAPRS), a specific binding peptide targeting mouse CD133, was screened and identified for the first time by phage-displayed peptide library technology. The in vitro and in vivo affinity and specificity of LS-7 were determined, and MTT, adhesion, and migration assays were performed to evaluate the effects of LS-7 on the biological behaviors of cancer cells. To determine which signaling pathways are affected by LS-7, HMGB1, S-100A4, CXCR7, uPAR... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5581002 Sat, 07 Jan 2012 16:52:13 +0100 5581002 http://www.medworm.com/index.php?rid=5581003&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frt4314637786421t%2F Abstract  ST6GalNAcI is a sialyltransferase responsible for the synthesis of sialyl Tn (sTn) antigen which is expressed in a variety of adenocarcinomas including gastric cancer especially in advanced cases, but the roles of ST6GalNAcI and sTn in cancer progression are largely unknown. We generated sTn-expressing human gastric cancer cells by ectopic expression of ST6GalNAcI to evaluate metastatic ability of these cells and prognostic effect of ST6GalNAcI and sTn in a mouse model, and identified sTn carrier proteins to gain insight into the function of ST6GalNAcI and sTn in gastric cancer progression. A green fluorescent protein-tagged human gastric cancer cell line was transfected with ST6GalNAcI to produce sTn-expressing cells, which were transplanted into nude mice. STn-po... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5581003 Sat, 07 Jan 2012 16:52:12 +0100 5581003 http://www.medworm.com/index.php?rid=5544165&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F27784qu51231801j%2F We describe the generation of two orthotopic murine models for endometrial cancer (EC).The first model is generated from endometrial Hec-1A cancer cells transfected with luciferase and injected directly into the uterus of female mice. This model allows a follow-up with bioluminescence imaging (BLI) along the experiment and generates abdominal dissemination and lymphatic and hematogenous metastases in high percentages, also detectables with BLI. The dissemination pattern of this model imitates the advanced stages of EC in patients, and its molecular profile corresponds to aggressive type 2 EC (p53 positive, hormone receptors negative, high percentage of Ki67 positive cells). The second model is derived from endometrioid human tissue collected from surgical pieces. By injecting this ti... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5544165 Sat, 24 Dec 2011 16:45:43 +0100 5544165 http://www.medworm.com/index.php?rid=5515052&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F945l8284l0678122%2F In conclusion, EBRT with ≤60 Gy appears to be a good palliative therapy with reasonable safety for patients with pulmonary metastases from HCC. However, large-scale randomized clinical trials will be necessary to confirm the therapeutic role of this method. Content Type Journal ArticleCategory Research PaperPages 1-9DOI 10.1007/s10585-011-9442-4Authors Wei Jiang, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032 ChinaZhao-Chong Zeng, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032 ChinaJian-Ying Zhang, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032 ChinaJia Fan, Liver Cancer Institute, Zho... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5515052 Thu, 15 Dec 2011 16:51:12 +0100 5515052 http://www.medworm.com/index.php?rid=5515053&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm28264v058140102%2F Abstract  Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs) show dramatic antitumor activity in a subset of patients with non-small cell lung cancer who have an active mutation in the epidermal growth factor receptor (EGFR) gene. On the other hand, some lung cancer patients with wild type EGFR also respond to EGFR–TKIs, suggesting that EGFR–TKIs have an effect on host cells as well as tumor cells. However, the effect of EGFR–TKIs on host microenvironments is largely unknown. A multiple organ metastasis model was previously established in natural killer cell-depleted severe combined immunodeficient mice using human lung cancer cells. This model was used to investigate the therapeutic efficacy of erlotinib, an EGFR–TKI, on multiple organ meta... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5515053 Wed, 14 Dec 2011 16:43:08 +0100 5515053 http://www.medworm.com/index.php?rid=5515054&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl76v40234l877ng5%2F Abstract  Although previous studies demonstrated anticancer activities of gossypol through the induction of apoptosis, the molecular mechanism(s) responsible for the inhibitory effects of gossypol on the metastatic behavior of cancer cells remain to be elucidated. Here, we show that gossypol inhibits growth of human prostate cancer cells through the modulation of cell cycle regulatory proteins. We also demonstrate that gossypol inhibits invasive behaviors (adhesion, migration, and invasion) and angiogenesis. These effects are mediated by the suppression of AP-1 and NF-κB activity, resulting in the inhibition of secretion of urokinase plasminogen activator and vascular endothelial growth factor, and the down-regulation of expression of chemokine receptor 4 in PC3 cells. In ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5515054 Tue, 13 Dec 2011 17:02:28 +0100 5515054 http://www.medworm.com/index.php?rid=5476158&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh1275341011l7mp3%2F In conclusion, the present findings suggest that SRC inhibition by dasatinib may have utility in reducing the metastatic spread of prostate cancer cells. Content Type Journal ArticleCategory Research PaperPages 1-10DOI 10.1007/s10585-011-9436-2Authors Lori Rice, Department of Radiation Oncology, University of Florida, 2033 Mowry Rd. CGRC, Rm 485E, Gainesville, FL 32610, USASharon Lepler, Department of Radiation Oncology, University of Florida, 2033 Mowry Rd. CGRC, Rm 485E, Gainesville, FL 32610, USAChristina Pampo, Department of Radiation Oncology, University of Florida, 2033 Mowry Rd. CGRC, Rm 485E, Gainesville, FL 32610, USADietmar W. Siemann, Department of Radiation Oncology, University of Florida, 2033 Mowry Rd. CGRC, Rm 485E, Gainesville, FL 32610, USA Journal Clinical ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5476158 Wed, 30 Nov 2011 18:39:45 +0100 5476158 http://www.medworm.com/index.php?rid=5468414&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr50h6601655t4w22%2F Abstract  Bone sialoprotein (BSP) regulates bone metabolism by directly influencing the activity of osteoblasts and osteoclasts. A significant correlation between the tissue expression of BSP in tumors and the occurrence of bone metastases was found in different cancers. Aim of this study was to identify the BSP expression in renal cell carcinomas (RCC) according to their stage of metastatic disease. Tissue samples of patients with RCC who underwent partial resection or nephrectomy were separated into three groups, each with 10 patients showing either no metastases (group I), only soft tissue metastases (group II) or bone metastases (group III) at date of surgery. Immunohistochemical analysis of BSP expression in tumor tissue and corresponding renal parenchyma was performed... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5468414 Wed, 30 Nov 2011 18:39:45 +0100 5468414 http://www.medworm.com/index.php?rid=5449537&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F03xgp0tn480613u3%2F Abstract  Bone is a major target for metastases in the most frequent solid tumors, which result in severe complications and are a major cause of pain. A bone metastasis gene expression signature was identified using human breast cancer cells in a mouse model. The bone metastasis-related genes encode secretory and cell surface proteins implicated in bone-homing (CXCR4), angiogenesis (CTGF and FGF5), invasion (MMP-1 and ADAMTS1), and osteoclast recruitment (IL11). This signature superimposes on the 70-gene poor prognosis gene expression signature for breast cancer, and only ADAMTS1, CTGF and IL11 were found to be overexpressed in human primary breast cancers with bone relapse. We analyzed the expression of the six bone metastasis-related genes in bone metastases from patients wi... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5449537 Fri, 25 Nov 2011 17:57:12 +0100 5449537 http://www.medworm.com/index.php?rid=5449538&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp108567154236353%2F Abstract  MicroRNAs (miRs) are short non-coding RNAs that bind complementary sequences in mRNA resulting in translation repression and/or mRNA degradation. We investigated expression of the reported metastasis-associated miRs-335, 206, 135a, 146a, 146b, 10b, 21, let7a and let7b in normal mucosa, non-metastatic and metastatic colorectal cancer (CRC). Expression of target miRs in micro-dissected paraffin embedded tissues was evaluated in 15 primary tumours with adjacent normal tissue from patients that were disease-free at 4 years (cohort A) and 19 paired primary tumours with corresponding liver metastases (cohort B) by quantitative real-time PCR. Increased expression of miR-21, mir-135a and miR-335 was associated with clinical progression of CRC, while miR-206 demonstrat... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5449538 Fri, 25 Nov 2011 17:57:09 +0100 5449538 http://www.medworm.com/index.php?rid=5449539&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwx1734215t707m30%2F Abstract  Almost half of breast Ductal Carcinoma in situ are likely to remain non threatening in situ lesions with no invasion to the surrounding stroma and no metastases. The majority of focal disruptions in myoepithelial (ME) cell layers indicative of invasion onset were found to be overlying epithelial cell clusters with no or substantially reduced estrogen receptor α (ERα) expression. Here we report the down-regulation of tyrosine kinase-2 (TYK2) and up-regulation of strumpellin expression, among other proteins in ERα(−) cells located at disrupted ME layers compared to adjacent ERα(+) cells overlying an intact myoepithelial layer. ERα(+) and ERα(−) cells were microdissected from the same in vivo human breast cancer tissues, proteins were extracted and separate... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5449539 Thu, 24 Nov 2011 17:52:36 +0100 5449539 http://www.medworm.com/index.php?rid=5407155&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F127h047n2275qt12%2F In conclusion, the localization and the functionality of Cx43 may govern the ability of PCa cells to metastasize in bones. Content Type Journal ArticleCategory Research PaperPages 1-12DOI 10.1007/s10585-011-9434-4Authors Coralie Lamiche, CNRS, UMR6187, Institute of Cellular Physiology and Biology, University of Poitiers, Bat. B36, 1, rue G. Bonnet, BP 633, 86022 Poitiers Cedex, FranceJonathan Clarhaut, CNRS, UMR6187, Institute of Cellular Physiology and Biology, University of Poitiers, Bat. B36, 1, rue G. Bonnet, BP 633, 86022 Poitiers Cedex, FrancePierre-Olivier Strale, CNRS, UMR6187, Institute of Cellular Physiology and Biology, University of Poitiers, Bat. B36, 1, rue G. Bonnet, BP 633, 86022 Poitiers Cedex, FranceSophie Crespin, CNRS, UMR6187, Institute of Cellular Physiology a... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5407155 Fri, 11 Nov 2011 12:50:01 +0100 5407155 http://www.medworm.com/index.php?rid=5407156&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F40241l80n2u83788%2F Abstract  Interaction between CXCR4 and CXCL12 plays a role in tumor progression. The present study examined CXCR4, CXCL12 and CD133 expression in liver metastases of colorectal cancer (CLM) and determined whether the expression profiles affect the tumor microenvironment and thus progression, and whether they could serve as a prognostic marker for survival. Liver metastases of colorectal cancer collected from 92 patients were evaluated by CXCR4, CXCL12 and CD133 immunohistochemistry and clinicopathological data were analyzed. The expression profile of CXCR4 was determined in the colorectal cancer cell line, SW48. The expression of cytoplasmic CXCR4 was higher in 36 (39%) patients than that indicated by CXCR4 staining intensity of hepatocytes. High levels of nuclear CXCR4 ex... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5407156 Thu, 10 Nov 2011 16:52:21 +0100 5407156 http://www.medworm.com/index.php?rid=5384586&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F47m8147238601272%2F Abstract  Unresectable colorectal liver metastases are commonly treated with systemic chemotherapy (SCT). Clinical studies on the effect of additional systemic application of bevacizumab (BE), a monoclonal antibody directed against vascular endothelial growth factor, to SCT showed a slight increase of patient survival. Herein, we studied in a rat model of colorectal liver metastasis whether a locoregional application of oxaliplatin (OX) and BE via hepatic arterial infusion (HAI) is more effective to inhibit metastatic growth compared to systemic drug application. Ten days after implantation of CC531 colorectal cancer cells into the left liver lobe of WAG/Rij rats, animals underwent either HAI or systemic intravenous application of BE (5 mg/kg body weight), OX (85 ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5384586 Thu, 03 Nov 2011 16:58:21 +0100 5384586 http://www.medworm.com/index.php?rid=5384585&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc2t5450804750863%2F Abstract  Synthetic oligodeoxynucleotides containing CpG motifs (CpG DNA) can activate immunocompetent cells, which may possess antitumor activity. Previously, we found that when the cationic liposomes complexes formed with CpG DNA (CpG DNA lipoplex) were administered intranasally, they could prevent pulmonary metastasis in mice. However, the mechanisms underlying this process are unknown. In the present study, we show that natural killer (NK) cells play an important role in preventing pulmonary metastasis and peritoneal dissemination in a mouse model of metastatic disease. Further, in vitro, the NK cells obtained from mice treated with CpG DNA lipoplex showed higher cytotoxicity compared with untreated mice and in vivo, depletion of NK cells (achieved through injection of ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5384585 Thu, 03 Nov 2011 16:58:21 +0100 5384585 http://www.medworm.com/index.php?rid=5384587&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb7h8359108074882%2F This study aimed to identify diagnostic value of survivin protein in malignant pleural effusion (MPE) and to investigate the prediction of response to chemotherapy and the prognostic role on pleural survivin in lung cancer patients with MPE. Pleural effusion samples were collected from 67 patients with MPE (58 lung cancers; 9 extrathoracic tumors), and from 68 patients with benign conditions (31 with pneumonia; 37 with tuberculosis). Concentrations of pleural fluid survivin, Cyfra 21-1, and carcinoembryonic antigen (CEA) were measured by enzyme-linked immunosorbent assay. The expression profile of survivin in pleural fluid, and its association with survival, were investigated. Survivin levels were significantly elevated in patients with MPE, especially primary lung cancer than in th... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5384587 Tue, 01 Nov 2011 16:52:36 +0100 5384587 http://www.medworm.com/index.php?rid=5384588&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft4221jx75r7457jt%2F Abstract  Epigenetic drugs such as histone deacetylase inhibitors (HDACIs) possess anticancer properties due to its ability to regulate genes associated with tumor growth, differentiation, apoptosis and metastasis. In addition to its apoptotic effect, phenylbutyrate (PB), a carboxylic acid HDACI, inhibited an anaplastic (ATC) thyroid cancer cell line ARO from penetrating a matrigel coated transwell with concomitant suppression of a metastasis-associated gene, matrix metalloproteinase-7 (MMP-7) and stimulation of a transformation suppressor protein, reversion-inducing- cysteine-rich protein with Kazal motifs without affecting MMP-2 expression levels. Direct evidence suggesting MMP-7 down-regulated cancer metastasis came from the observation of a decreased pulmonary metastasi... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5384588 Tue, 01 Nov 2011 05:54:17 +0100 5384588 http://www.medworm.com/index.php?rid=5384589&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj663k57u83180221%2F Abstract  Pharmacological approaches to treat breast cancer metastases in the brain have been met with limited success. In part, the impermeability of the blood brain barrier (BBB) has hindered delivery of chemotherapeutic agents to metastatic tumors in the brain. BBB-permeable chemotherapeutic drugs are being developed, and noninvasively assessing the efficacy of these agents will be important in both preclinical and clinical settings. In this regard, dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) are magnetic resonance imaging (MRI) techniques to monitor tumor vascular permeability and cellularity, respectively. In a rat model of metastatic breast cancer, we demonstrate that brain and bone metastases develop with distinct physiological characteristic... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5384589 Mon, 31 Oct 2011 16:59:23 +0100 5384589 http://www.medworm.com/index.php?rid=5313888&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6xx4l01757822m8h%2F Abstract  Hypoxia and its down-stream activated pathways are commonly involved in tumor progression. Genes involved in angiogenesis and glycolysis, i.e. vascular endothelial growth factor (VEGF) and lactase dehydrogenase A (LDHA), respectively, are transcriptionally controlled by the hypoxia inducible factors 1α and 2α (HIF1α and HIF2α). A series of 60 uveal melanomas were immunohistochemically assessed for the expression of VEGF and the phosphorylated/activated form of VEGF receptor 2 (pVEGFR2/KDR), after binding to VEGF. The expression of HIF1α, HIF2α and LDH5 was also investigated. Uveal melanomas overexpressing HIF2α (but not that of HIF1α) were significantly associated with high VEGF (P = 0.005), pVEGFR2/KDR (P < 0.0001) and LDH5 (P �... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5313888 Sat, 08 Oct 2011 15:44:20 +0100 5313888 http://www.medworm.com/index.php?rid=5304088&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqq3112q3488r6g14%2F Abstract  CD24 is a glycosyl-phosphatidylinositol-anchored protein with mucin-type structure that resides exclusively in membrane microdomains. CD24 is often highly expressed in carcinomas and correlates with poor prognosis. Experimentally, the over-expression or depletion of CD24 alters cell proliferation, adhesion, and invasion in vitro and tumor growth in vivo. However, little is known about the mechanisms by which CD24 mediates these cellular effects. Here we have studied the mechanism of CD24-dependent cell invasion using transient CD24 knock-down or over-expression in human cancer cell lines. We show that CD24 depletion reduced tumor cell invasion and up-regulated expression of Tissue Factor Pathway Inhibitor 2 (TFPI-2), a potent inhibitor of extracellular matrix degr... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5304088 Fri, 07 Oct 2011 15:59:57 +0100 5304088 http://www.medworm.com/index.php?rid=5285172&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb68568872k3lm8p1%2F In this study, we show that this E-cadherin re-expression confers a survival advantage, particularly in the liver microenvironment. E-cadherin re-expression in MDA-MB-231 breast cancer cells resulted in increased attachment to hepatocytes. This heterotypic adhesion between cancer cells and secondary organ parenchymal cells activated ERK MAP kinase, suggesting a functional pro-survival role for E-cadherin during metastatic colonization of the liver. In addition, breast cancer cells that re-expressed E-cadherin in hepatocyte coculture were more chemoresistant compared to 231-shEcad cells unable to re-express E-cadherin. Similar results were obtained in DU-145 prostate cancer cells induced to re-express E-cadherin in hepatocyte coculture or following chemical induction by the GnRH agoni... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5285172 Sun, 02 Oct 2011 05:47:30 +0100 5285172 http://www.medworm.com/index.php?rid=5273238&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq20234k3774qt413%2F Abstract  Few therapeutic strategies exist for the treatment of metastatic tumor cells in the brain because the blood–brain barrier (BBB) limits drug access. Thus the identification of molecular targets and accompanying BBB permeable drugs will significantly benefit brain metastasis patients. Polo-like kinase 1 (Plk1) is an attractive molecular target because it is only expressed in dividing cells and its expression is upregulated in many tumors. Analysis of a publicly available database of human breast cancer metastases revealed Plk1 mRNA expression was significantly increased in brain metastases compared to systemic metastases (P = 0.0018). The selective Plk1 inhibitor, GSK461364A, showed substantial uptake in normal rodent brain. Using a breast cancer brain m... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5273238 Wed, 28 Sep 2011 05:48:31 +0100 5273238 http://www.medworm.com/index.php?rid=5273239&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy073377016414l1m%2F Abstract  CD44 plays an important role in cancer metastasis, chemotherapy, and radiation resistance. The present study investigated the relationship of CD44 expression and radioresistance, and the potential mechanisms of CD44 in radiosensitivity using prostate cancer (CaP) cell lines. CD44 was knocked down in three CaP cell lines (PC-3, PC-3M-luc, and LNCaP) using small interfering RNA (siRNA) and clonogenic survival fractions after single dose irradiation were compared before and after CD44 knocking down (KD). The effect of radiation on cell cycle distribution was examined by flow cytometry and the cell cycle-related protein levels of phospho-Chk1 and phospho-Chk2 were ascertained by Western blotting. The expression of the DNA double strand break (DSB) marker-γH2AX was al... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5273239 Wed, 28 Sep 2011 05:48:28 +0100 5273239 http://www.medworm.com/index.php?rid=5273240&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff2tuh5025v3755v2%2F In this study, we sequenced the catalytic domains of the three other members of the EGFR family, HER2, HER3, and HER4 in 92 clinical samples of HNSCC. We identified a HER2 mutation (K716E) in one sample but no mutations were found in HER3 or HER4. Next to investigate the relationship between EGFR mutations and tumor metastasis, we compared the DNA sequences of the EGFR gene between the primary tumor and the lymph node metastasis in 31 clinical samples. Only one of the patients with an EGFR mutation in the primary HNSCC carried the same mutation (L858R) in the lymph node metastasis. Finally, we explored the tumorigenic potential of the EGFR mutations that we had previously identified and their sensitivity to two different EGFR tyrosine kinase inhibitors (CL-387785, OSI-420). Ba/F3 ce... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5273240 Wed, 28 Sep 2011 05:48:27 +0100 5273240 http://www.medworm.com/index.php?rid=5260152&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe0508h55573ujg15%2F Abstract  The basement membrane protein laminin-511 has been implicated in breast cancer progression and metastasis. To identify peptides from LM-511 that modulate the metastatic properties of breast tumours, we screened laminin alpha 5 chain-derived peptides for their ability to promote adhesion of metastatic mammary carcinoma cells. Two selected adhesive peptides, α5A13b (FHVAYVLIKF) from the LN domain and A5G27 (RLVSYNGIIFFLK) from the LG-globular domain, were further characterised for their inhibitory properties against LM-511 activities in vitro and metastasis in vivo. In vitro, these peptides strongly inhibited LM-511-dependent adhesion and migration of highly metastatic 4T1.2 mammary carcinoma cells. In addition, A5G27 but not α5A13b significantly reduced breast tu... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5260152 Wed, 21 Sep 2011 16:24:55 +0100 5260152 http://www.medworm.com/index.php?rid=5207908&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7556160272250704%2F This article discusses the role of carcinoembryonic antigen (CEA) as a facilitator of the inflammatory response and its effect on colorectal cancer hepatic metastasis. Colorectal cancer accounts for 11% of all cancers in the United States and the majority of deaths are associated with liver metastasis. If left untreated, median survival is only six to 12 months. Resection of liver metastases offers the only chance for cure. Of the small number of patients who have operable cancer most will have further tumor recurrence. The molecular mechanisms associated with colorectal cancer metastasis to the liver are largely unknown. However CEA production has been shown both clinically and experimentally to be a factor in an increased metastatic potential of colorectal cancers to the liver... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5207908 Thu, 08 Sep 2011 05:57:42 +0100 5207908 http://www.medworm.com/index.php?rid=5196098&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa7742m0672vu5407%2F In this study, overexpression of IL6Rα, and to a lesser extent IL6, enhanced tumor growth on the omentum. Moreover, adherence to plastic and to peritoneal extracellular matrix components was enhanced in tumor cells overexpressing IL6 or IL6Rα. Host production of IL6 and IL6Rα was also sufficient to influence tumor adherence to the omentum. Expression of LY75/CD205/DEC205, a collagen-binding mannose family receptor, was directly influenced by IL6Rα expression. Blocking LY75 with antibody reduced the adherence of tumor cells overexpressing IL6Rα to matrices in vitro and to the omentum. The association between IL6Rα expression and LY75 expression has not been previously reported, and the promotion of cellular adherence is a novel role for LY75. These studies indicate that overexpr... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5196098 Fri, 02 Sep 2011 05:47:39 +0100 5196098 http://www.medworm.com/index.php?rid=5183336&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw65t551556771372%2F Abstract  In 2009, malignant melanoma was responsible for approximately 9,000 deaths in the US. These deaths are often associated with aggressive metastasis to secondary sites such as the lungs. Epidemiological and animal studies suggest that obesity is a risk factor for melanoma. Others have shown that B16BL6 melanoma cells metastasize more aggressively in obese ob/ob than in lean mice. However, the mechanism by which obesity promotes B16BL6 melanoma metastasis in ob/ob mice has not been identified. In the present study, we used serum obtained from control and ob/ob leptin-deficient obese mice to determine if obese serum increases the aggressive phenotype of melanoma cells. Results showed that ob/ob serum has higher levels of resistin, insulin, tPAI1, IL-6, TNF-α, and MCP... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5183336 Tue, 30 Aug 2011 15:59:54 +0100 5183336 http://www.medworm.com/index.php?rid=5161045&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg7563488k1542018%2F Abstract  The tumor microenvironment is acidic as a consequence of upregulated glycolysis and poor perfusion and this acidity, in turn, promotes invasion and metastasis. We have recently demonstrated that chronic consumption of sodium bicarbonate increased tumor pH and reduced spontaneous and experimental metastases. This occurred without affecting systemic pH, which was compensated. Additionally, these prior data did not rule out the possibility that bicarbonate was working though effects on carbonic anhydrase, and not as a buffer per se. Here, we present evidence that chronic ingestion of a non-volatile buffer, 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA) with a pK a of 6.9 also reduced metastasis in an experimental PC3M prostate cancer mouse model. Animals (n&n... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5161045 Tue, 23 Aug 2011 05:56:37 +0100 5161045 http://www.medworm.com/index.php?rid=5143181&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flg043142705k13m5%2F In conclusion, this work suggests that forcing cells away from glycolysis may inhibit key components of the metastatic phenotype, providing a novel avenue for metastasis prevention. Content Type Journal ArticleCategory Research PaperPages 1-11DOI 10.1007/s10585-011-9417-5Authors Joseph L. Sottnik, Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523-1620, USAJanet C. Lori, Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523-1620, USABarbara J. Rose, Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523-1620, USADouglas H. Thamm, Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 8... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5143181 Sun, 14 Aug 2011 05:45:04 +0100 5143181 http://www.medworm.com/index.php?rid=5143182&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk502320626343172%2F Abstract  The poor prognosis and recurrence of HCC are majorly caused by intrahepatic metastasis. Delineating the molecular pathways mediating these processes may benefit developing effective targeting therapies. Using human hepatoma HepG2 as a model, we have found reactive oxygen species (ROS) may cooperate with protein kinase C (PKC) for sustained ERK phosphorylation and migration of HepG2 induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We further investigated whether integrin signaling is involved. Various antagonists of integrin signaling prevented TPA-induced activation of ERK and PKC, ROS generation and migration of HepG2. On the other hand, TPA-induced phosphorylation of integrin signaling components including focal adhesion kinase (FAK), Src (Tyr416) and pax... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5143182 Sun, 14 Aug 2011 05:45:02 +0100 5143182 http://www.medworm.com/index.php?rid=5131713&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F37465786708j0261%2F Abstract  We studied the expression pattern and the role of CD44 in regulating the malignant behavior of two cholangiocarcinoma (CCA) cell lines which expressed different levels of CD44 using the siRNA technique. KKU-100, the high CD44 expresser, exhibited a high degree of in vitro invasiveness, migration and adhesion to Matrigel compared to HuCCA-1. Silencing of CD44 by siRNA did not have a significant effect on cell proliferation. However, in vitro invasiveness, directional migration (chemotaxis) and adhesion to Matrigel were markedly reduced in both cell lines, although chemokinesis and MMP secretion were variable, demonstrating the distinct functional role and requirement for CD44 in different cellular activities and in different cell types. In addition, immunohistochem... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5131713 Thu, 11 Aug 2011 06:57:15 +0100 5131713 http://www.medworm.com/index.php?rid=5087244&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F95724050k28j6k24%2F Abstract  The volume doubling time (VDT) is an accurate and reproducible method for the quantitation of the rate and pattern of tumor growth in individual patients. The purpose of this study is to investigate the tumor VDT using chest CT in individual sarcoma patients with lung metastasis and to determine whether VDT is associated with survival after lung metastasis in bone and soft tissue sarcomas. Forty patients had measurable lung metastases in at least two sequential chest CT images taken at least 14 days apart. The VDT was calculated using the method originally described by Schwartz. The median and mean VDT in all 40 patients was 21.5 and 53 days, respectively. Similarly, the median and average VDT in 29 soft tissue sarcoma patients was 26 and 57 days, r... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5087244 Fri, 29 Jul 2011 16:06:22 +0100 5087244 http://www.medworm.com/index.php?rid=5087245&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F93g8j34606nl2363%2F Abstract  Lung cancer comprises a large variety of histological subtypes with a frequent proclivity to form bone metastasis; a condition associated with dismal prognosis. To identify common mechanisms in the development of osteolytic metastasis, we systematically screened a battery of lung cancer cell lines and developed three models of non-small cell lung cancer (NSCLC) with a common proclivity to form osseous lesions, which represented different histological subtypes. Comparative analysis revealed different incidences and latency times. These differences were correlated with cell-type-specific secretion of osteoclastogenic factors, including macrophage inflammatory protein-1α, interleukin-8 and parathyroid hormone-related protein, some of which were exacerbated in condit... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5087245 Wed, 27 Jul 2011 15:52:28 +0100 5087245 http://www.medworm.com/index.php?rid=5087248&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk7wu8793674ru21m%2F In conclusion, EMT occurs in human breast cancer in a manner distinct to that seen in vitro. Certain EMT events are uncoupled from E-cadherin down-regulation and may constitute a novel EMT profile, which warrants further exploration. Content Type Journal ArticlePages 1-8DOI 10.1007/s10585-011-9412-xAuthors Sylvie Dubois-Marshall, Breakthrough Breast Cancer Research Unit and Division of Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU UKJeremy S. Thomas, Breakthrough Breast Cancer Research Unit and Division of Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU UKDana Faratian, Breakthrough Breast Cancer Research Unit and Division ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5087248 Tue, 26 Jul 2011 05:54:46 +0100 5087248 http://www.medworm.com/index.php?rid=5087246&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu97366620k35q965%2F In conclusion, these findings show that tumor cell-derived Timp-1 acts as a positive regulator of the metastatic potential and support the concept that proteases and their natural inhibitors, as members of the protease web, are major players of signaling during normal homeostasis and disease. Content Type Journal ArticlePages 1-10DOI 10.1007/s10585-011-9410-zAuthors Florian Schelter, Institut für Experimentelle Onkologie und Therapieforschung des Klinikums rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 Munich, GermanyMartina Grandl, Institut für Experimentelle Onkologie und Therapieforschung des Klinikums rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 Munich, GermanyBastian Seubert, Institut für Experimentelle On... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5087246 Tue, 26 Jul 2011 05:54:46 +0100 5087246 http://www.medworm.com/index.php?rid=5063323&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg9j772t33857156k%2F Abstract  Bone is the third most common site of cancer metastasis. Over 30 to 40% of lung cancers can develop skeletal metastasis and no effective curative therapy exists in clinic cases. Previously we screened the different expression of proteins between SBC-5 cells and SBC-3 cells by proteomic study methods (MALDI-TOF/TOF-MS) and found that calcineurin (hereafter referred as Cn) overexpresses in SBC-5 which has special priority in metastasis to bone in a multiple-organ metastasis mice model. However the roles of Cn in osteotropism of SCLC remain to be elucidated. At present study, we decrease CnAα expression in SBC-5 by lentiviral vector-mediated RNAi and found that down regulation of CnAα gene expression can decrease the proliferation and colony formation rate, impede ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5063323 Fri, 22 Jul 2011 16:59:41 +0100 5063323 http://www.medworm.com/index.php?rid=5063324&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F154u1275w50w5362%2F Abstract  Radiotherapy induces untargeted effects on normal tissues such as bone marrow. So alteration of microenvironment by ionizing irradiation is supposed to influence dynamic host-cancer ecosystem affecting cancer behavior including metastasis. Herein, the incidence of lung metastasis after high-dose irradiation has been investigated using mice model having real-time condition of leucopenia. C57BL/6 mice were pre-exposed to a X-irradiation dose of 6 Gy on previous days 2, 5, 7, 10. Complete hematological parameters including lymphocyte subpopulation in blood and lung tissues were analyzed. Additionally, a group of mice including a non-irradiated group were inoculated with B16F10 cells (3 × 105/200 μl) via tail vein at the same day, and lung metasta... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5063324 Tue, 19 Jul 2011 06:43:10 +0100 5063324 http://www.medworm.com/index.php?rid=5030062&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk455204m6282q646%2F This study employed gastric cancer cells and patient tissues in attempts to elucidate how and why this mutation in galectin-3 (gal-3H64) enhances cancer progression, compared to wild type galectin-3 (gal-3P64). First, we prepared lenti-virus constructs containing gal-3P64, gal-3H64 and LacZ, and used them to infect galectin-3 null SNU-638 cells. We found that gal-3H64 over-expression increases gastric cancer cell growth more than gal-3P64 or LacZ over-expression. Also, gal-3H64 over-expression conferred more resistance to cisplatin or 5-FU induced cytotoxicity than gal-3P64. Gal-3H64 also enhanced nuclear accumulation of β-catenin as well as increased expression of TCF-4 target genes, such as fascin-1 and c-Myc through the augmented promoter binding activity of TCF-4, than gal-3P64. We ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5030062 Wed, 13 Jul 2011 06:03:28 +0100 5030062 http://www.medworm.com/index.php?rid=5030061&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu47275h3l6524108%2F In conclusion, these data demonstrated for the first time that CD133+CD44+ SLCCs were highly enriched in HCT116 cells and that metastatic SLCCs resided exclusively in a CD133+CD44high subpopulation. Content Type Journal ArticlePages 1-13DOI 10.1007/s10585-011-9407-7Authors Ke-li Chen, Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaFeng Pan, Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaHeng Jiang, Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaJian-fang Chen, Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaLi Pei, Department of Oncology, Southwest Hospital, Third Mil... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5030061 Wed, 13 Jul 2011 06:03:28 +0100 5030061 http://www.medworm.com/index.php?rid=5030063&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff67xl61273498868%2F Abstract  Advanced hepatocellular carcinoma (HCC) is an important cause of cancer mortality. Epithelial-mesenchymal transition (EMT) has been shown to be an important biological process in cancer progression and metastasis. We have focused on elucidating factors that induce EMT to promote carcinogenesis and subsequent metastasis in HCC using the BNL CL.2 (BNL) and BNL 1ME A. 7R.1 (1MEA) cell lines. BNL cells are normal hepatocytes whereas the 1MEA cells are HCC cells derived from chemical transformation of the BNL cells. Their morphological characteristics were examined. Expression levels of hepatocyte growth factor (HGF), markers of EMT and mediators of HGF signaling were determined and functional characteristics were compared. BNL cells were treated with HGF and effects o... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5030063 Sun, 10 Jul 2011 05:49:40 +0100 5030063 http://www.medworm.com/index.php?rid=5020068&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgh68l452156531h8%2F Abstract  We previously described a lipid-accumulating phenotype of estrogen receptor negative (ER−) breast cancer cells exemplified by the MDA-MB-231 and MDA-MB-436 cell lines. These cells had more lipid droplets, a higher uptake of oleic acid and LDL, a higher ratio of cholesteryl ester (CE) to triacylglycerol (TAG), and higher expression of acyl-CoA:cholesterol acyltransferase 1 (ACAT1) as compared to ER+ MCF-7 breast cancer cells. LDL stimulated proliferation of ER-cells only, and proliferation was reduced by inhibition of ACAT. We hypothesized that storage of exogenous lipids would confer an energetic advantage. We tested this by depriving cells of exogenous lipids and measuring chemotactic migration, an energy-intensive behavior. MDA-MB-231 cells were grown for 4... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5020068 Sat, 09 Jul 2011 06:18:34 +0100 5020068 http://www.medworm.com/index.php?rid=5020069&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw865875881266862%2F Abstract  Milk fat is a natural product containing essential nutrients as well as fatty acids and other food factors with reported anti-cancer potential. Here bovine milk fat was tested for its ability to inhibit the growth of breast and colon cancers and their metastasis to the lung and liver; either alone or in combination with the chemotherapeutic agent paclitaxel. A diet containing 5% typical anhydrous milk fat (representing ~70% of the total dietary fat component) fed to Balb/c mice delayed the appearance of subcutaneous 4T1 breast and CT26 colon cancer tumours and inhibited their metastasis to the lung and liver, when compared to the control diet containing soybean oil as the only fat component. It augmented the inhibitory effects of paclitaxel on tumour growth and me... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5020069 Fri, 08 Jul 2011 06:36:13 +0100 5020069 http://www.medworm.com/index.php?rid=5020070&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqv8p55x15v876228%2F Abstract  Toll-like receptors (TLRs) are members of transmembrane proteins that recognize conserved molecular motifs of viral and bacterial origin and initiate innate immune response. As the role of TLRs in tumors cells is still not clear, our aim was to investigate the role of TLR3 in primary tumor and metastatic cells (SW480, SW620, FaDu and Detroit 562). We have reported here on the dual role of TLR3 in pharynx metastatic cell line (Detroit 562); on one hand TLR3 activation drove cells to apoptosis while on the other its stimulation contributed to tumor progression by altering the expression of tumor promoting genes (PLAUR, RORB) and enhancing the cell migration potential. In addition, we have shown TLR3 signaling pathway is functional in another metastatic cancer cell li... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5020070 Thu, 07 Jul 2011 05:42:54 +0100 5020070 http://www.medworm.com/index.php?rid=5020071&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F03867r4234205m5w%2F Abstract  The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye IRDye®800CW, tested their selectivity, sensitivity and biological activity in vitro and their feasibility to visualize tumors in vivo. Purified CXCL12-conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7 breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was time- and concentration-dependent, and the label could be competitively displ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=5020071 Thu, 07 Jul 2011 05:42:52 +0100 5020071 http://www.medworm.com/index.php?rid=4998474&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff36881r3314843ru%2F Abstract  We evaluated the expression of tissue factor (TF) in ovarian cancer (EOC) and the potential of hI-con1, an antibody-like molecule targeting TF, as a novel form of therapy against chemotherapy-resistant ovarian disease. We studied the expression of TF in 88 EOC by immunohistochemistry (IHC) and real-time-PCR (qRT-PCR) and the levels of membrane-bound-complement-regulatory-proteins CD46, CD55 and CD59 in primary EOC cell lines by flow-cytometry. Sensitivity to hI-con1-dependent-cell-mediated-cytotoxicity (IDCC), complement-dependent-cell-cytotoxicity and inhibition of IDCC by γ-immunoglobulin were evaluated in 5-h 51chromium-release-assays. Cytoplasmic and/or membrane TF expression was observed in 24 out of 25 (96%) of the EOC samples tested by IHC, but not in norma... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4998474 Fri, 01 Jul 2011 17:42:40 +0100 4998474 http://www.medworm.com/index.php?rid=4993543&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0192m03442n42w48%2F Abstract  The stroma of hepatocellular carcinoma (HCC) is markedly infiltrated with activated hepatic stellate cells (HSCs), and associated invasion and metastasis of HCC. However, little is known of the role of HSCs in immune responses in HCC. The Buffalo rat HCC model was established. Quiescent HSCs (qHSCs) and intratumoral HSCs (tHSCs) were isolated. Surface molecules of tHSC were detected by flow cytometry, and gene expression was analyzed by fluorescence quantitative RT-PCR. T cell proliferation was monitored by [3H]-thymidine (3H-TdR) incorporation into DNA, and cytotoxic activity was assessed by measuring the release of 51Cr. The level of cytokine expression by T cells was measured by enzyme-linked immunosorbent assay. T cell apoptosis was detected by double-stained t... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4993543 Wed, 29 Jun 2011 10:51:47 +0100 4993543 http://www.medworm.com/index.php?rid=4960660&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh353814r738vrm11%2F In conclusion, erlotinib inhibits tumor-induced osteolytic invasion in bone metastasis by suppressing osteoclast activation through inhibiting tumor growth at the bone metastatic sites, osteolytic factor production in tumor cells, osteoblast/stromal cell proliferation and osteoclast differentiation from mouse bone marrow cells. Content Type Journal ArticlePages 1-11DOI 10.1007/s10585-011-9398-4Authors Koh Furugaki, Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, JapanYoichiro Moriya, Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, JapanToshiki Iwai, Product Research Department, Kamakura Research Laborator... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4960660 Mon, 20 Jun 2011 14:21:25 +0100 4960660 http://www.medworm.com/index.php?rid=4946318&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F96304w535266n238%2F Abstract  A characteristic of human gastroenteropancreatic neuroendocrine tumors (GEP-NET) is a minute unobtrusive primary tumor which often cannot be detected by common physical examinations. It therefore remains unidentified until the tumor has spread and space-occupying metastases cause clinical symptoms leading to diagnosis. Cases in which the primary cannot be located are referred to as NET with CUP-syndrome (cancer of unknown primary syndrome). With the help of array-CGH (comparative genomic hybridization, Agilent 105K) and gene expression analysis (Agilent 44K), microdissected primaries and their metastases were compared to identify up- and down-regulated genes which can be used as a marker for tumor progression. In a next analysis step, a hierarchical clustering of ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4946318 Fri, 17 Jun 2011 10:58:33 +0100 4946318 http://www.medworm.com/index.php?rid=4936253&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd0m197h823610132%2F Abstract  The small guanosine triphosphatase (GTPase) Rho and its downstream effector Rho-associated kinase (ROCK) is one of a key mediator involved in controlling focal adhesions and the dynamics of actin stress fibers. The molecular mechanisms for the function of Rho/ROCK pathway leading to the progression in scirrhous gastric carcinoma cells have not been defined. The activation of RhoA in several gastric carcinoma cells was examined. The role of RhoA/ROCK pathway in the metastatic processes of gastric carcinoma cells, using a human scirrhous gastric cancer cell line, OCUM-2MD3 was investigated by in vitro adhesion and invasion assay. The effect of ROCK inhibitor, Y-27632 on the mRNA expression of the integrin family and MMP in gastric carcinoma cells was subsequently ex... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4936253 Sun, 12 Jun 2011 06:03:51 +0100 4936253 http://www.medworm.com/index.php?rid=4913241&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff7514143055n4522%2F In this study, we evaluated whether ALDH7A1 is required for the acquisition of a metastatic stem/progenitor cell phenotype in human prostate cancer. Knockdown of ALDH7A1 expression resulted in a decrease of the α2hi/αvhi/CD44+ stem/progenitor cell subpopulation in the human prostate cancer cell line PC-3M-Pro4. In addition, ALDH7A1 knockdown significantly inhibited the clonogenic and migratory ability of human prostate cancer cells in vitro. Furthermore, a number of genes/factors involved in migration, invasion and metastasis were affected including transcription factors (snail, snail2, and twist) and osteopontin, an ECM molecule involved in metastasis. Knockdown of ALDH7A1 resulted in decreased intra-bone growth and inhibited experimentally induced (bone) metastasis, while intra-pr... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4913241 Tue, 07 Jun 2011 05:49:26 +0100 4913241 http://www.medworm.com/index.php?rid=4913242&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft1580183m1544345%2F Abstract  The progression of cancer from non-metastatic to metastatic is the critical transition in the course of the disease. The epithelial to mesenchymal transition (EMT) is a mechanism by which tumor cells acquire characteristics that improve metastatic efficiency. Targeting EMT processes in patients is therefore a potential strategy to block the transition to metastatic cancer and improve patient outcome. To develop models of EMT applicable to in vitro and in vivo settings, we engineered NCI-H358 non-small cell lung carcinoma cells to inducibly express three well-established drivers of EMT: activated transforming growth factor β (aTGFβ), Snail or Zeb1. We characterized the morphological, molecular and phenotypic changes induced by each of the drivers and compared the... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4913242 Sat, 04 Jun 2011 06:06:04 +0100 4913242 http://www.medworm.com/index.php?rid=4903718&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6483645670375800%2F In this study, we aimed to investigate the role of DKK1 in ovarian serous papillary adenocarcinoma (OSC) tumor progression and invasion. Quantitative real-time RT–PCR and Western blot analysis showed that the expression of DKK1 mRNA and protein in 32 OSC tissues were elevated as compared with those in 10 normal ovarian tissues (P = 0.005, P = 0.003, respectively). Immunohistochemical analysis in 178 clinical OSC samples showed that the expression of DKK1 was positively associated with FIGO stage (P = 0.016). Furthermore, the expression of DKK1 protein was positively associated with P-JNK1 protein expression in 178 OSC tissues. DKK1, P-JNK1 and the co-expression of DKK1 and P-JNK1 were all unfavorable prognosis factors for OSC patients (P < ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4903718 Tue, 24 May 2011 05:53:31 +0100 4903718 http://www.medworm.com/index.php?rid=4903719&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F08j110hq76827676%2F Abstract  Fibroblast activation protein-α (FAP) is a cell surface, serine protease of the post-prolyl peptidase family that is expressed in human breast cancer but not in normal tissues. Previously, we showed that FAP expression increased tumor growth rates in a mouse model of human breast cancer. Here the role of the proteolytic activities of FAP in promoting tumor growth, matrix degradation and invasion was investigated. Mammary fat pads of female SCID mice were inoculated with breast cancer cells that express FAP and the mice treated with normal saline or Val-boroPro (talabostat); Glu-boroPro (PT-630); or 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine (LAF-237) that inhibit prolyl peptidases. Other mice were injected with breast cancer cells expressing a... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4903719 Sat, 21 May 2011 23:06:00 +0100 4903719 http://www.medworm.com/index.php?rid=4781997&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh7vnr8185n222921%2F In this study, the roles of the protein tyrosine kinases FAK and Pyk2 in EL4 phenotype were examined, with a particular emphasis on the role of these proteins in metastasis. FAK is expressed only in PMA-resistant (or intermediate phenotype) EL4 cells, correlating with enhanced cell–substrate adherence, while Pyk2 is more highly expressed in non-adherent PMA-sensitive cells. PMA treatment causes modulation of mRNA for FAK (up-regulation) and Pyk2 (down-regulation) in PMA-sensitive but not PMA-resistant EL4 cells. The increase in Pyk2 mRNA is correlated with an increase in Pyk2 protein expression. The roles of FAK in cell phenotype were further explored using transfection and knockdown experiments. The results showed that FAK does not play a major role in modulating PMA-induced Erk a... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4781997 Sun, 01 May 2011 05:42:44 +0100 4781997 http://www.medworm.com/index.php?rid=4781998&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9m157nm672429010%2F Abstract  Tumor biomarkers assist in the early detection of cancer, act as therapeutic targets for intervention, and function as diagnostic indicators for the evaluation of therapeutic responses. To identify novel human breast cancer biomarkers, we have analyzed the protein content of lipid rafts isolated from a series of human mammary epithelial cell lines with increasing tumorigenic potential. Since lipid rafts function as platforms for protein interaction critical to several biological processes, we hypothesized that the abundance of proteins associated with proliferation, invasion and metastasis would be dysregulated in highly transformed cells. For this purpose, the MCF10A epithelial lineage, which include benign MCF10A cells, premalignant AT and TG3B cells, and malign... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4781998 Sun, 01 May 2011 05:42:43 +0100 4781998 http://www.medworm.com/index.php?rid=4781999&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpgg1834j12413133%2F We examined the level of RGS22 expression by tumor tissue arrays, immunohistochemistry and by analyzing the expression levels of four human esophageal cancer cell lines with different metastatic potential using western blot. In addition, we examined the role of RGS22 over-expression in the processes of invasion and metastasis using a highly metastatic cancer cell line. We show that RGS22 are expressed in many tumor types, but specific to cancers with epithelial origin and associated with cancer metastasis. In addition, we identified the association of RGS22 to tumor invasion in cancer cell lines. Over-expression of RGS22 in a highly metastatic esophageal cancer cell line causes decrease in cell migration and reduction in the invasive potential of the cells. RGS22 is over-expressed i... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4781999 Sat, 30 Apr 2011 23:41:40 +0100 4781999 http://www.medworm.com/index.php?rid=4709844&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr414723701185845%2F Abstract  Mena, an actin regulatory protein, functions at the convergence of motility pathways that drive breast cancer cell invasion and migration in vivo. The tumor microenvironment spontaneously induces both increased expression of the Mena invasive (MenaINV) and decreased expression of Mena11a isoforms in invasive and migratory tumor cells. Tumor cells with this Mena expression pattern participate with macrophages in migration and intravasation in mouse mammary tumors in vivo. Consistent with these findings, anatomical sites containing tumor cells with high levels of Mena expression associated with perivascular macrophages were identified in human invasive ductal breast carcinomas and called TMEM. The number of TMEM sites positively correlated with the development of dis... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4709844 Mon, 11 Apr 2011 15:54:19 +0100 4709844 http://www.medworm.com/index.php?rid=4709845&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4p350184414m2176%2F In conclusion, MG63 cell line appears to induce a significant paracrine-mediated osteoclastogenic response. Understanding the mechanisms underlying the interaction of osteosarcoma cells and osteoclasts may contribute to the development of new potential approaches in the treatment of such bone metabolic diseases. Content Type Journal ArticlePages 1-10DOI 10.1007/s10585-011-9387-7Authors J. Costa-Rodrigues, Laboratório de Farmacologia e Biocompatibilidade Celular, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393, Porto, PortugalC. A. Teixeira, Laboratório de Farmacologia e Biocompatibilidade Celular, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393, Porto, PortugalM. H. Fernandes, Lab... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4709845 Fri, 08 Apr 2011 20:56:50 +0100 4709845 http://www.medworm.com/index.php?rid=4685803&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff7524w2872458002%2F Abstract  Discoidin domain receptors (DDRs) are receptor tyrosine kinases that get activated by collagens in its native triple-helical form. In mammalian cells, DDR family consists of two members, namely DDR1 and DDR2, which mediates migration and proliferation of several cell types. DDR1 is activated by native type IV collagen and overexpressed in human breast cancer. Type IV collagen is the main component of basement membrane (BM), and the ability to degrade and penetrate BM is related with an increased potential for invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that collectively are capable of degrading all components of the extracellular matrix, including the BM. In breast cancer cells, denatured type IV collagen... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4685803 Sun, 03 Apr 2011 05:43:49 +0100 4685803 http://www.medworm.com/index.php?rid=4685804&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4136512641456514%2F Abstract  Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4685804 Sat, 02 Apr 2011 05:50:18 +0100 4685804 http://www.medworm.com/index.php?rid=4671300&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F422w07290655240h%2F Abstract  The concept of molecular tumor targeting might provide new hope in the treatment of advanced prostate cancer. We evaluated metastasis blocking properties of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and the mammalian target of rapamycin (mTOR) inhibitor RAD001 on prostate cancer cell lines. RAD001 or VPA were applied to PC-3 or LNCaP cells, either separately or in combination. Adhesion to vascular endothelium or to immobilized collagen, fibronectin or laminin was quantified. Migration and invasion were explored by a modified Boyden chamber assay. Integrin α and β subtypes were analyzed by flow cytometry, western blotting and RT-PCR. Effects of drug treatment on integrin related signaling, Akt and p70S6kinase activation, histone H3 and H4 acety... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4671300 Thu, 31 Mar 2011 07:20:15 +0100 4671300 http://www.medworm.com/index.php?rid=4654175&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx6396197u7476022%2F Abstract  Gli1 is an established oncogene and its expression in Estrogen Receptor (ER) α negative and triple negative breast cancers is predictive of a poor prognosis; however, the biological functions regulated by Gli1 in breast cancer have not been extensively evaluated. Herein, Gli1 was over-expressed or down-regulated (by RNA interference and by expression of the repressor form of Gli3) in the ERα negative, human breast cancer cell lines MDA-MB-231 and SUM1315. Reduced expression of Gli1 in these two cell lines resulted in a decrease in migration and invasion. Gli1 over-expression increased the migration and invasion of MDA-MB-231 cells with a corresponding increase in expression of MMP-11. Silencing MMP-11 in MDA-MB-231 cells that over-expressed Gli1 abrogated the Gl... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4654175 Sun, 27 Mar 2011 05:46:19 +0100 4654175 http://www.medworm.com/index.php?rid=4654174&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7585qkn06t37562g%2F Abstract  Galectin-3, a β galactoside–binding lectin, plays an important role in the processes relevant to tumorigenesis such as malignant cell transformation, invasion and metastasis. We have investigated whether deletion of Galectin-3 in the host affects the metastasis of B16F1 malignant melanoma. Galectin-3-deficient (Gal-3−/−) mice are more resistant to metastatic malignant melanoma as evaluated by number and size of metastatic colonies in the lung. In vitro assays showed lower number of attached malignant cells in the tissue section derived from Gal-3−/− mice. Furthermore, lack of Galectin-3 correlates with higher serum levels of IFN-γ and IL-17 in tumor bearing hosts. Interestingly, spleens of Gal-3−/− mice have lower number of Foxp3+ T cells after injec... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4654174 Sun, 27 Mar 2011 05:46:19 +0100 4654174 http://www.medworm.com/index.php?rid=4561410&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F258u53x20784726n%2F Abstract  Intratumor heterogeneity—heterogeneity of cancer cells within a single tumor—is considered one of the most problematic factors of treatment. Genetic heterogeneity, such as in somatic mutations and chromosome aberrations, is a common characteristic of human solid tumors and is probably the basis of biological heterogeneity. Using mutations in APC, TP53 and KRAS as markers to identify distinct colorectal cancer subpopulations, we analyzed a total of 42 primary colorectal cancer tissues and six paired liver metastases with multipoint microsampling, which enabled analysis of mutation patterns and allelic imbalances with a resolution of 0.01 mm2 (about 200 cells). There was usually more than one subpopulation in each primary tumor. Only two of 15 (13.3%) cases w... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4561410 Fri, 04 Mar 2011 16:47:18 +0100 4561410 http://www.medworm.com/index.php?rid=4561411&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq3176124mp715kx8%2F Abstract  Osteosarcoma (OSA) is an aggressive, highly metastatic and lytic primary bone neoplasm commonly affecting the appendicular skeleton of dogs and children. Current treatment options include amputation of the afflicted limb, limb-sparing procedures, or palliative radiation with or without adjunct chemotherapy. Therapies that inhibit bone resorption, such as the bisphosphonates, may be an effective palliative therapy by limiting the local progression of OSA in those patients that are not viable candidates for amputation. We have developed a mouse model of canine skeletal OSA following intratibial inoculation of OSCA40 cells that spontaneously metastasized to the lungs. We demonstrated that therapy with a nitrogen-containing bisphosphonate, zoledronic acid (Zol), reduc... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4561411 Fri, 04 Mar 2011 10:49:35 +0100 4561411 http://www.medworm.com/index.php?rid=4561412&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg721573127421304%2F Abstract  Accumulation of fibroblasts is a phenomenon that significantly correlates with formation of aggressive cancers. While studies have shown that the TGF-β signaling pathway is an important regulator of fibroblast activation, the functional contribution of TGF-β signaling in fibroblasts during multi-step tumor progression remains largely unclear. In previous studies, we used a sub-renal capsule transplantation model to demonstrate that homozygous knockout of the Tgfbr2 gene (Tgbr2FspKO) enhanced mammary tumor growth and metastasis. Here, we show for the first time a significant role for loss of one Tgfbr2 allele during multi-step mammary tumor progression. Heterozygous deletion of Tgfbr2 in stromal cells in MMTV–PyVmT transgenic mice (PyVmT/Tgfbr2hetFspKO mice) resul... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4561412 Fri, 04 Mar 2011 10:49:34 +0100 4561412 http://www.medworm.com/index.php?rid=4550181&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk138248u7536t427%2F Abstract  We retrospectively analyzed treatment outcomes and factors for poor prognosis for patients with renal cell cancer (RCC) bone metastases. Patients with bone metastases at initial diagnosis of metastasis secondary from RCC, treated at our hospital between 1984 and 2009, were retrospectively reviewed and statistically analyzed. Among 214 RCC patients with metastasis, 71 patients (33%) were found to have bone metastases at initial diagnosis of metastasis. The median follow-up was 21.1 months (intra-quartile range: IQR, 9.1–47.4 months). The estimated median overall survival time from the diagnosis of bone metastasis was 27.7 months. The probability of patients surviving at 1, 2, and 5 years was 63.7, 52.2, and 19.3%, respectively. When they were s... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4550181 Wed, 02 Mar 2011 07:48:10 +0100 4550181 http://www.medworm.com/index.php?rid=4550180&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk187290p82384146%2F In conclusion, annexin A1 expression correlated with tumor stage, lymph node metastasis, relapse, and patient survival. Annexin A1 is proposed to function importantly in the progression of lung AdC. Content Type Journal ArticlePages 1-13DOI 10.1007/s10585-011-9380-1Authors Ying-Fu Liu, Department of Basic Medical Sciences, Medical College, Xiamen University, 168# Daxue Road, Xiamen, 361005 Fujian ChinaPeng-Fei Zhang, Key Laboratory of Cancer Proteomics of Ministry of Health, Central South University, 87# Xiangya Road, Changsha, 410008 Hunan ChinaMao-Yu Li, Key Laboratory of Cancer Proteomics of Ministry of Health, Central South University, 87# Xiangya Road, Changsha, 410008 Hunan ChinaQuo-Qing Li, Key Laboratory of Cancer Proteomics of Ministry of Health, Central South University, ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4550180 Wed, 02 Mar 2011 07:48:10 +0100 4550180 http://www.medworm.com/index.php?rid=4513147&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5m748440k3g7p430%2F Abstract  As a member of adherens junction, p120-catenin (p120ctn) plays a major role in cell adhesions through stabilization of E-cadherin. p120ctn is transcriptionally down-regulated in non-small cell lung cancer (NSCLC), although the molecular mechanisms underlying p120ctn repression are incompletely defined. Here we further investigated transcriptional regulation of p120ctn in NSCLC. We prepared a promoter reporter plasmid construct that contained p120ctn promoter region from position −1082 to +320 relative to transcription start site. Through serial deletion mutation analysis of the p120ctn promoter, we pinpointed cis-acting elements involved in regulation of p120ctn. We identified transcription factor SP1 as a transcriptional repressor of p120ctn that directly binds to ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4513147 Sat, 19 Feb 2011 18:24:54 +0100 4513147 http://www.medworm.com/index.php?rid=4502527&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3818007668138382%2F Abstract  Pancreatic cancer demonstrates a strong resistance to anticancer drugs, presumably due to its resistance to drug induced apoptosis. Although gemcitabine (GEM) might be partially effective for treating advanced pancreatic cancer, its efficacy is still less than satisfactory. Galectin-3 (gal-3), a member of the β-galactoside-binding protein family, is a multifunctional protein with roles in tumor cell adhesion, proliferation, differentiation, angiogenesis, metastasis, and apoptosis. We have utilized gal-3 small interfering RNA (siRNA) to probe whether gal-3 regulates anticancer drug-induced apoptosis in pancreatic cancer cells. We found that Gal-3 siRNA augmented GEM- and cisplatin-induced apoptosis in pancreatic cancer cell lines in vitro. Mitochondrial depolariza... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4502527 Thu, 17 Feb 2011 17:01:32 +0100 4502527 http://www.medworm.com/index.php?rid=4471071&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk7654712020757qk%2F Abstract  The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material studied for prognosis is either, cutaneous primaries or metastatic deposits, rather than t... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4471071 Thu, 10 Feb 2011 19:57:32 +0100 4471071 http://www.medworm.com/index.php?rid=4442638&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd4v806k62021762h%2F Abstract  There is accumulating evidence that secondary plant metabolites such as flavonoids may have anti-cancer properties, and yet the molecular pathways that lead to alterations in cancer cell behaviour remain unclear. We investigated the possible actions of apigenin, a flavone present in leafy vegetables like parsley, on the levels of CD26 in carcinoma cells. CD26 is a multifunctional cell-surface protein that through its associated dipeptidyl peptidase (DPPIV) and ecto-adenosine deaminase (eADA) enzyme activities is able to suppress pathways involved in tumour metastasis. CD26 is down-regulated in various cancers including colorectal carcinoma. Apigenin substantially up-regulated cell-surface CD26 on HT-29 and HRT-18 human colorectal cancer cells. Levels of CD26 ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4442638 Fri, 04 Feb 2011 17:36:46 +0100 4442638 http://www.medworm.com/index.php?rid=4400575&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp3jj135187015433%2F Abstract  Germline mutations affecting the retinoblastoma gene (RB1) predispose to inherited retinoblastomas but also other malignancies, including breast cancer. While somatic RB1 mutations have been detected in different malignancies, information about the potential role of RB1 mutations in breast cancer is limited. Recently, we discovered RB1 mutations to be associated with resistance to anthracyclines/mitomycin in primary breast cancer. The present work is the first report evaluating RB1 mutation and epigenetic status in metastatic breast cancer. Among 148 breast cancer samples analyzed by MLPA, four samples harbored intragenic deletions/duplications: Thus, exons 1–2 were deleted in two tumors and exons 21–23 in one tumor, while one sample harbored duplication of exons... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4400575 Fri, 21 Jan 2011 15:21:48 +0100 4400575 http://www.medworm.com/index.php?rid=4356253&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy1p2605ml8q10134%2F We examined metastasis in common gamma-chain (γC) KO mice, which are deficient in NK, NKT and CD8+ T cells, and in Vα14Jα281−/− KO mice, which are deficient in invariant NKT (iNKT) cells, in order to assess the importance of specific IFN-γ producing cell types to this effect. We found that the antimetastatic effect of alcohol was still present in γC KO mice and also in γC KO mice depleted of Gr-1+ cells. Knockout of iNKT cells reduced the degree but not the antimetastatic effect associated with alcohol. These results indicate that the antimetastatic effect induced by chronic alcohol consumption is IFN-γ dependent and that multiple IFN-γ producing cell types contribute to this effect. Content Type Journal ArticlePages 1-7DOI 10.1007/s10585-011-9372-1Authors Hui Zhang... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4356253 Fri, 14 Jan 2011 14:14:36 +0100 4356253 http://www.medworm.com/index.php?rid=4356254&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn134072j705tj391%2F This study demonstrates that CDDO-Im may be useful for the treatment metastatic liver disease as it successfully inhibits growth of actively proliferating liver metastases. Content Type Journal ArticlePages 1-9DOI 10.1007/s10585-011-9374-zAuthors Jason L. Townson, London Regional Cancer Program, 790 Commissioners Road East, Office A4-903B, London, ON N6A 4L6, CanadaIan C. MacDonald, Department of Medical Biophysics, University of Western Ontario, London, ON CanadaKaren T. Liby, Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH USALisa Mackenzie, Department of Medical Biophysics, University of Western Ontario, London, ON CanadaDavid W. Dales, London Regional Cancer Program, 790 Commissioners Road East, Office A4-903B, London, ON N6A 4L6, CanadaBenjamin... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4356254 Fri, 14 Jan 2011 14:14:32 +0100 4356254 http://www.medworm.com/index.php?rid=4322908&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjwx73n6731541261%2F In this study, we developed a mouse model for GCPM, and investigated electrophysiological changes in the small intestine and attendant changes in ICC. We found decreased ICC and disrupted electrical rhythm in the model. Pathologic ICC changes were well described. Cancer peritoneal metastasis may impair intestinal myoelectrical activity by damaging ICC and ICC networks. Interstitial cells of Cajal will be a target of palliative treatment and merit further study. Content Type Journal ArticlePages 1-9DOI 10.1007/s10585-010-9371-7Authors Hongqun Zheng, Department of Oncology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, Yiyuan Street, Nangang District, Harbin, ChinaYan He, Department of Pathology, Harbin Medical University, 157 Baojian Road, Nangang District, ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4322908 Wed, 05 Jan 2011 06:45:36 +0100 4322908 http://www.medworm.com/index.php?rid=4319170&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe231q551254x1427%2F Abstract  We analysed population-based treatment and survival data of patients who presented with metastatic rectal cancer. All patients diagnosed with primary synchronous metastatic rectal cancer between 1992 and 2008 in the Eindhoven Cancer Registry area were included. Date of diagnosis was divided into three periods (1992–1999, 2000–2004, 2005–2008) according to the availability of chemotherapy type. We assessed treatment patterns and overall survival according to period of diagnosis. The proportion of patients diagnosed with stage IV disease increased from 16% in 1992–1999 to 20% in 2005–2008 (P < 0.0001). Chemotherapy use increased from 5% in 1992 to 61% in 2008 (P < 0.0001). Resection rates of the primary tumour decreased from 65% in ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4319170 Tue, 04 Jan 2011 17:53:11 +0100 4319170 http://www.medworm.com/index.php?rid=4319171&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr627172h2535h214%2F Abstract  HER receptor family plays an important role in normal embryonic development and is involved in pathogenesis and progression of some types of cancer. Neuroblastic tumors (NT) are common pediatric neoplasms with a poor outcome in a significant number of patients. The biological and prognostic role of HER family in NT is not well established. In the current study we evaluated HER1–4 receptors expression, their prognostic significance and clinicopathological correlations in a series of 103 NTs by immunohistochemical assessment of HER1–4 expression and FISH analysis of EGFR and HER2 copy number status. HER receptors are commonly expressed in NT but it was not due to EGFR or HER2 amplification. EGFR, HER2 and HER4 show correlation with tumor histology. It seems that... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4319171 Tue, 04 Jan 2011 07:40:04 +0100 4319171 http://www.medworm.com/index.php?rid=4302353&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv160x44w307xn457%2F Abtract  Epithelial–mesenchymal transition (EMT) is an important contributor to the invasion and metastasis of epithelial-derived cancers. While considerable effort has focused in the regulators involved in the transition process, we have focused on consequences of EMT to prosurvival signaling. Changes in distinct metastable and ‘epigentically-fixed’ EMT states were measured by correlation of protein, phosphoprotein, phosphopeptide and RNA transcript abundance. The assembly of 1167 modulated components into functional systems or machines simplified biological understanding and increased prediction confidence highlighting four functional groups: cell adhesion and migration, metabolism, transcription nodes and proliferation/survival networks. A coordinate metabolic reduc... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4302353 Thu, 30 Dec 2010 18:04:12 +0100 4302353 http://www.medworm.com/index.php?rid=4289090&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1v4u5m8244540777%2F In conclusion we observed unique histone modifications in two colon cancer cell lines with different metastatic potentials, indicating possible mechanisms for the down-regulation of NDRG1 in metastatic SW620. Content Type Journal ArticleDOI 10.1007/s10585-010-9366-4Authors Qian Li, Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Bevier Hall 472, 905 S. Goodwin Ave., MC-182, Urbana, IL 61801, USAHong Chen, Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Bevier Hall 472, 905 S. Goodwin Ave., MC-182, Urbana, IL 61801, USA Journal Clinical and Experimental MetastasisOnline ISSN 1573-7276Print ISSN 0262-0898 (Source: Clinical and Experimental Metastasis) Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4289090 Thu, 23 Dec 2010 17:48:56 +0100 4289090 http://www.medworm.com/index.php?rid=4289092&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0085353tn744542t%2F Abstract  Transmembrane protein tetraspanins either promote or suppress tumor invasion and metastasis. Their effects on tumor progression depend on the multimolecular transmembrane complex called tetraspanin-enriched microdomain (TEM) and are attributed to the alterations in the (1) motogenic and mitogenic behaviors and/or (2) microenvironmental interactions of tumor cells. As the modifiers of cell membrane structure and function, tetraspanins have emerged as diagnostic and prognostic markers and therapeutic targets for tumor progression. Content Type Journal ArticleDOI 10.1007/s10585-010-9365-5Authors Mekel M. Richardson, Vascular Biology Center, University of Tennessee Health Science Center, H300 Coleman Building, 956 Court Avenue, Memphis, TN 38163, USALisa K. Jenni... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4289092 Thu, 23 Dec 2010 17:48:54 +0100 4289092 http://www.medworm.com/index.php?rid=4289091&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg061656l2r4xr413%2F Content Type Journal ArticleDOI 10.1007/s10585-010-9361-9 Journal Clinical and Experimental MetastasisOnline ISSN 1573-7276Print ISSN 0262-0898 (Source: Clinical and Experimental Metastasis) Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4289091 Thu, 23 Dec 2010 17:48:54 +0100 4289091 http://www.medworm.com/index.php?rid=4267028&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F557gg67772324w58%2F In this study, we investigated whether treatment with recombinant versican could induce the formation of a pericellular matrix by ovarian cancer cells (OVCAR-3, OVCAR-5, and SKOV-3) and promote their motility, invasion, and adhesion to peritoneal cells in vitro. We also determined whether versican-induced pericellular matrix formation and metastatic cancer cell behavior could be blocked by small HA oligosaccharides. Only combined treatment with recombinant versican and HA resulted in pericellular matrix formation by OVCAR-5 and SKOV-3 but not by OVCAR-3 cells, which lack the HA receptor, CD44. The motility of OVCAR-5 and SKOV-3 cells was significantly increased in scratch wound and chemotaxis assays following treatment with recombinant versican and HA. Versican and HA also promoted i... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4267028 Mon, 13 Dec 2010 22:04:50 +0100 4267028 http://www.medworm.com/index.php?rid=4197756&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2h22qt13u3590263%2F Abstract  Two-dimensional isoelectric focusing and gel electrophoresis followed by mass spectrometry were used to detect, measure, and identify changes in protein expression correlated with differences in the metastatic potential of cultured rat mammary adenocarcinoma cells. MTC is a non-metastatic cell clone derived from a primary tumor. MTLn2 and MTLn3 are low and high metastatic potential cell clones derived from lung metastases of the primary tumor. A total of 1,500 proteins was detected. The patterns of protein expression of MTLn2 and MTLn3 cells were similar. Only five spots had a threefold or greater statistically significant difference in staining intensity between MTLn2 and MTLn3 cells, whereas 70 spots differed between MTC and MTLn3 cells. Twenty spots were select... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4197756 Mon, 22 Nov 2010 16:45:21 +0100 4197756 http://www.medworm.com/index.php?rid=4164776&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb18587r00882m050%2F Abstract  Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4164776 Thu, 11 Nov 2010 06:54:37 +0100 4164776 http://www.medworm.com/index.php?rid=4155802&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwg1n8473p1g23570%2F Abstract  To investigate the relevant molecular mechanisms of platelet in promoting metastasis of tumor cell. The adhesion of fluorescence dye labeled-platelet to human liver sinusoidal endothelial cell (LSEC) line and tumor cell lines were detected by fluorescence microscope and fluorescence plate reader or laser scanning confocal microscope. The relevant adhesion molecules were analyzed by the antibody blockage experiment. The immune colloidal gold transmission electron microscope (TEM), flow cytometry and dye transfer were used to decipher the adhesion and fusion of platelet and LSEC. The tumor cells adhesion to vessels in ischemia condition was analyzed on mouse mesenteric vessels and the metastasis and neovascularization of metastatic foci in pulmonary tissue were also... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4155802 Tue, 09 Nov 2010 07:50:43 +0100 4155802 http://www.medworm.com/index.php?rid=4140965&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F771x57q328r1gw75%2F Abstract  The “protease web”, representing the network of proteases, their inhibitors, and effector molecules, arises as a pivotal determinant of tissue homeostasis. Imbalances of this network, for instance caused by elevated host levels of tissue inhibitor of metalloproteinases-1 (TIMP-1), have been shown to increase the susceptibility of target organs to scattered metastasis by inducing the hepatocyte growth factor (HGF) pathway. Increased expression of the hypoxia-inducible factor-1α-subunit (HIF-1α) is also associated with tumour progression and is also known to induce HGF-signaling via up-regulation of the HGF-receptor Met, namely under canonical stress conditions like lack of oxygen. Here, we aimed to identify a possible metastasis-promoting connection between TI... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4140965 Thu, 04 Nov 2010 17:49:27 +0100 4140965 http://www.medworm.com/index.php?rid=4120379&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F275380432q5567j1%2F This study sought to investigate the effect of endoglin on these parameters. We used a murine orthotopic model of human PCa metastasis, designed by us to measure effects at early steps in the metastatic cascade, and implanted PCa cells stably engineered to express differing levels of endoglin. We now extend this model to measure cancer cells circulating in the blood. Progressive endoglin loss led to progressive increases in the number of circulating PCa cells as well as to the formation of soft tissue metastases. Endoglin was known to suppress invasion by activating the Smad1 transcription factor. We now show that it selectively activates specific Smad1-responsive genes, including JUNB, STAT1, and SOX4. Increased tumor growth and increased Ki67 expression in tissue was seen only with... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4120379 Wed, 27 Oct 2010 16:06:41 +0100 4120379 http://www.medworm.com/index.php?rid=4120378&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa54162330288j0r7%2F Abstract  Several data of the past years clearly indicated that the fusion of tumor cells and tumor cells or tumor cells and normal cells can give rise to hybrids cells exhibited novel properties such as an increased malignancy, drug resistance, or resistance to apoptosis. In the present study we characterized hybrid cells derived from spontaneous fusion events between the breast epithelial cell line M13SV1-EGFP-Neo and two breast cancer cell lines: HS578T-Hyg and MDA-MB-435-Hyg. Short-tandem-repeat analysis revealed an overlap of parental alleles in all hybrid cells indicating that hybrid cells originated from real cell fusion events. RealTime-PCR-array gene expression data provided evidence that each hybrid cell clone exhibited a unique gene expression pattern, resulting ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4120378 Wed, 27 Oct 2010 16:06:41 +0100 4120378 http://www.medworm.com/index.php?rid=4089267&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F92487276168kp410%2F In this study, expression of TRAP protein and enzymatic activity in bone metastases from different primary sites was examined. TRAP activity was high in bone metastases from prostate cancer, intermediate in breast cancer, and low in lung and kidney cancers. The partially purified TRAP from breast cancer bone metastasis samples exhibited the enzymatic characteristics of purple acid phosphatase. Both 5a and 5b isoforms were expressed in bone metastases of different histogenetic origins, i.e. prostate, breast, lung and kidney, and also a novel previously unreported 42 kDa variant of the TRAP 5a isoform was identified in bone metastases. This novel TRAP 5a isoform was absent in human bone, indicating that the 42 kDa variant is specific to metastatic cancer tissue. Immunohistoch... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4089267 Thu, 21 Oct 2010 17:16:33 +0100 4089267 http://www.medworm.com/index.php?rid=4089268&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb27700702964303p%2F Abstract  Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated s... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4089268 Wed, 20 Oct 2010 17:58:26 +0100 4089268 http://www.medworm.com/index.php?rid=4089269&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F324484212222j187%2F Abstract  The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mou... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4089269 Sat, 16 Oct 2010 17:55:11 +0100 4089269 http://www.medworm.com/index.php?rid=4004693&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F64836151349wn622%2F Abstract  The outcomes of osteosarcoma patients still remain poor because of intractable pulmonary metastasis. We previously established a highly metastatic osteosarcoma cell line, LM8 from Dunn mouse osteosarcoma by in vivo selection. We herein aimed to clarify the characteristic biological features related with high metastatic potential and new target molecules to suppress pulmonary metastasis of osteosarcoma, using this syngeneic spontaneous metastatic model. LM8 cells acquired fibroblastic morphology with striking filopodia on the cell surface. Immunostaining showed faint stress fiber formation and peripherally localized integrin β1, and biochemical analyses showed the activated Cdc42 and autophosphorylation of focal adhesion kinase (FAK) in LM8 cells when compared to ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=4004693 Sat, 25 Sep 2010 16:59:49 +0100 4004693 http://www.medworm.com/index.php?rid=3977905&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F56186n287774713k%2F In conclusion, the present study shows total p-AKT overexpression to be more frequent in metastases than in PRCCs. Total p-AKT overexpression in metastases without concomitant overexpression in their primary tumors was found in approximately one-third of primary onset metastases, which is interesting with regard to the association between high p-AKT expression and sensitivity to mTOR inhibitor therapy. Content Type Journal ArticleDOI 10.1007/s10585-010-9351-yAuthors Martina Hager, Department of Pathology, Paracelsus Medical University (PMU), Salzburg, AustriaHeike Haufe, Department of Pathology, Paracelsus Medical University (PMU), Salzburg, AustriaLukas Lusuardi, Department of Urology, Paracelsus Medical University (PMU), Salzburg, AustriaNikolaus Schmeller, Department of Urolog... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3977905 Thu, 16 Sep 2010 05:54:08 +0100 3977905 http://www.medworm.com/index.php?rid=3977906&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv48r208060567u06%2F Abstract  Identifying molecular targets for treatment of pancreatic cancer metastasis is critical due to the high frequency of dissemination prior to diagnosis of this lethal disease. Because the KISS1 metastasis suppressor is expressed at reduced levels in advanced pancreatic cancer, we hypothesized that re-expression of KISS1 would reduce metastases. Highly metastatic S2VP10 cells expressing luciferase (S2VP10L) were transfected with a FLAG-tagged version of KISS1 (KFM), KFMΔSS (with deleted secretion signal sequence), or pcDNA3 control plasmid (CP) and expression was confirmed by RTQ-PCR. SCID mice were implanted orthotopically with S2VP10L cells or transfectants and tumor growth and metastases were monitored using bioluminescence imaging. Mice with S2VP10L-KISS1 tumors... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3977906 Wed, 15 Sep 2010 16:57:06 +0100 3977906 http://www.medworm.com/index.php?rid=3947701&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp0p712p11n74m817%2F Abstract  Angiogenesis is induced by soluble factors such as vascular endothelial growth factor (VEGF) released from tumor cells in hypoxia. It enhances solid tumor growth and provides an ability to establish metastasis at peripheral sites by tumor cell migration. Thymosin beta-4 (TB4) is an actin-sequestering protein to control cytoskeletal reorganization. Here, we investigated whether angiogenesis and tumor metastasis are dependent on hypoxia conditioning-induced TB4 expression in B16F10 melanoma cells. TB4 expression in B16F10 cells was increased by hypoxia conditioning in a time-dependent manner. In addition, we found an increase of angiogenesis and HIF-1α expression in TB4-transgenic (Tg) mice as compared to wildtype mice. When wound healing assay was used to assess i... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3947701 Wed, 08 Sep 2010 05:20:16 +0100 3947701 http://www.medworm.com/index.php?rid=3873747&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn52u8273883lk218%2F Content Type Journal ArticleDOI 10.1007/s10585-010-9348-6Authors Adriana Albini, IRCCS MultiMedica, Milan, MI ItalyJózsef Tímár, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary Journal Clinical and Experimental MetastasisOnline ISSN 1573-7276Print ISSN 0262-0898 (Source: Clinical and Experimental Metastasis) Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3873747 Sat, 14 Aug 2010 08:38:27 +0100 3873747 http://www.medworm.com/index.php?rid=3865816&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcv92137507103100%2F Abstract  The present study assessed the effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice. Three-week old male C57BL/6 mice were fed the AIN-93G diet or a 45% fat diet (% kcal.) for 7 weeks before they were subcutaneously injected with 2.5 × 105 viable carcinoma cells. The primary tumor was resected 2 weeks later, and mice were maintained on their respective diets for an additional 2 weeks. The high-fat diet significantly increased body weight and abdominal adipose weight compared to the AIN-93G diet. Feeding mice the 45% fat diet resulted in a two-fold increase in the number of lung metastases (P < 0.05), a 35% increase in tumor cross-sectional area, and a 50% increase in tumor volume compared to mice fed... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3865816 Tue, 10 Aug 2010 19:28:20 +0100 3865816 http://www.medworm.com/index.php?rid=3824649&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy108p107777r7587%2F Abstract  Hepatopoietin Cn (HPPCn) is a novel nuclear protein with the ability to promote liver regeneration. In the present study, we investigated the expression profile of HPPCn and its functional activity in human hepatocellular carcinoma (HCC) cell line and tissue samples. HPPCn expression was detected in HCC cell lines and 54 paired HCC carcinomas by immunochemical staining and Western blotting. The functional activity of HPPCn in cell lines was evaluated by MTT and colony formation assays and with nude mouse model. The correlation of HPPCn expression with clinicopathological characteristics of 54 HCC patients was also analyzed. Our results showed that HPPCn protein was prominently located within the nuclei of hepatocytes and the expression level was evidently increase... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3824649 Wed, 04 Aug 2010 08:04:12 +0100 3824649 http://www.medworm.com/index.php?rid=3791760&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj8w3l06k80361813%2F Abstract  Cancer metastasis and anti-cancer drug resistance are the major reason for the failure of clinical cancer treatment. We evaluated CD147, monocarboxylate transporters (MCT1 and MCT4), and multidrug resistance (MDR) markers (MDR1 and MRP2) in 4 epithelial ovarian cancer (EOC) cell lines and primary tumors (n = 120) along with the matched metastatic lesions (n = 40) with immunofluorescence labeling. We correlated CD147 with MCT1, MCT4, MDR1 and MRP2 markers in primary and metastatic cells in cell lines and tissues using confocal microscopy. We also investigated the relationship of expression of CD147, MCT1 and MCT4 with various progression parameters. Our results indicate that the co-expression of CD147 with MCTs or MDR markers was found in primary... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3791760 Sat, 24 Jul 2010 13:47:32 +0100 3791760 http://www.medworm.com/index.php?rid=3773583&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw0365r846376g284%2F In this study, we investigated whether YM529/ONO-5920 inhibits tumor cell migration, invasion, adhesion, and metastasis in B16BL6 cells, a mouse melanoma cell line. It was found that YM529/ONO-5920 significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not show anti-proliferative effects on B16BL6 cells. YM529/ONO-5920 also inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs). Furthermore, YM529/ONO-5920 suppressed Rho activation, but not activation of Ras. The results indicate that YM529/ONO-5920 suppresses the Rho/ROCK pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion and metastasis. These findings suggest that YM529/ONO-5920 has potential clinical applications for the tre... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3773583 Fri, 16 Jul 2010 16:54:14 +0100 3773583 http://www.medworm.com/index.php?rid=3747721&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1443122338701nr8%2F Abstract  The clinical significance of circulating follistatin (FLST), an inhibitor of the multifunctional cytokine activin A (Act A), was investigated in patients with prostate cancer (PCa). The serum concentrations of this molecule were determined by an enzyme-linked immunosorbent assay (ELISA) in PCa patients with (M+) or without (M0) bone metastases, in patients with benign prostate hyperplasia (BPH) and in healthy subjects (HS). The effectiveness of FLST in detecting PCa patients with skeletal metastases was determined by the receiver operating characteristic (ROC) curve analysis. Serum FLST was significantly higher in PCa patients than in BPH patients (P = 0.001) or HS (P = 0.011). Conversely, in BPH patients, FLST levels resulted lower than in HS (... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3747721 Sun, 11 Jul 2010 12:16:14 +0100 3747721 http://www.medworm.com/index.php?rid=3747722&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3115538123432142%2F Abstract  Cancer cells metastasize by entering the lymphatic system. Regional lymph-node dissemination is the first detectable step in the metastasis of oral squamous cell carcinoma (SCC) and is highly correlated to the prognosis of the disease. Cold shock domain protein A (CSDA) is a DNA-binding protein that represses angiogenesis and lymphangiogenesis by directly binding to hypoxia response element (HRE) and serum response element (SRE). In our study we used the cell line NR-S1M, a mouse SCC model with a high rate of lymph-node metastasis. Into these cells we transfected the expression-plasmid coding for full-length mouse CSDA. Of importance, we showed that overexpression of CSDA significantly inhibits the production of VEGF-A and VEGF-C in NR-S1M cells. The overexpressio... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3747722 Sat, 10 Jul 2010 07:04:30 +0100 3747722 http://www.medworm.com/index.php?rid=3741591&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkt7881478831v747%2F Abstract  Single cell progenies (SCPs) inherit biological properties from their isogenetic mother cells. If a single cancer cell can give rise to progenies, which can be passaged sustainably in vitro and produce tumor in xenotransplantation, the cell should be cancer initiating cell. CD133 (Prominin-1, Prom1) is the marker of human colorectal cancer (CRC) stem cells and probably a marker of metastatic cancer stem cells (CSCs). Thirty-three SCPs of CRC cell line SW480 were isolated by limited dilution methods, thirty of which are CD133 positive and three negative. All of the CD133+ SCPs are tumorigenic, and the subcutaneous tumors expanded rapidly, while only 1 of 3 CD133− SCPs developed a minimal tumor in nude mice. Orthotopic transplantation experiments showed that CD133+ ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3741591 Fri, 09 Jul 2010 06:18:44 +0100 3741591 http://www.medworm.com/index.php?rid=3741592&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft946085l54842641%2F Abstract  Epidemiological and animal studies suggest an association between dietary fatty acids and an increase risk of developing breast cancer. Obesity, which is characterized by hyperlipidemia and an elevation of circulating free fatty acids (FFAs), is also associated with enhanced cancer risk. In breast cancer cells, the FFA oleic acid (OA) induces migration, proliferation, prolong survival, invasion, an increase in cellular Ca2+ concentration, MEK1/2, ERK1/2, FAK and Src activation. However, the role of OA on MMP-9 secretion and invasion has not been studied in detail. We demonstrate here that stimulation of MDA-MB-231 breast cancer cells with 200 μM OA induces an increase on MMP-9 secretion through a PKC, Src, and EGFR-dependent pathway, as revealed by gelatin zy... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3741592 Thu, 08 Jul 2010 16:18:56 +0100 3741592 http://www.medworm.com/index.php?rid=3734633&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx1tm206r88212532%2F Abstract  The rapidly evolving field of proteomics offers new approaches to understanding the pathogenesis of cancer and metastatic disease. Although numerous tumor markers have been identified with different genomic methods in the past, most are either not specific or sensitive enough to be used in routine clinical setting. The rationale for proteomic profiling is based on the fact that proteins represent the dynamic state of the cells, reflecting pathophysiological changes in the disease more accurately than genomic and epigenetic alterations. Emerging proteomic techniques allow simultaneous assessment of a large number of proteins at one time. The study of protein profiles in complex systems, such as plasma, serum or tissues of cancer patients is likely to become valuabl... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3734633 Wed, 07 Jul 2010 06:52:28 +0100 3734633 http://www.medworm.com/index.php?rid=3727634&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwqrh887k711729g0%2F Abstract  Ductal carcinoma in situ (DCIS) represents the earliest identifiable breast cancer lesion. Disruption of the myoepithelial cell layer and basement membrane is a prerequisite for DCIS to initiate invasion into the stroma. The majority of epithelial cells overlying a focally-disrupted myoepithelial cell layer are estrogen receptor-alpha negative (ER(−)); however, adjacent cells within the same duct confined by an intact myoepithelial cell layer express high levels of ER. These ER (+) and ER (−) cells were microdissected from the same ducts of breast cancer patients. Differential proteins expressed by ER(+) and ER(−) cells were identified using two-dimensional gel electrophoresis followed by mass spectrometry and Western blot analysis. ER(−) cells express low... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3727634 Sun, 04 Jul 2010 22:45:57 +0100 3727634 http://www.medworm.com/index.php?rid=3649663&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff0u8256np4w31v78%2F In this study, we investigated whether ERK regulates Rac1/Pak1 signaling and is critically linked to MB cell migration. Herein we demonstrate that PDGF-BB treatment of MB cells induces concomitant activation of PDGFRβ, MEK1/ERK, Rac1 and Pak1, but suppresses Rho activity, which together significantly promotes cell migration. Conversely, cells transfected with either PDGFRβ or Pak1 siRNA or treated with an inhibitor of Rac1 (NSC23766) or N-myristoyltransferase-1 (Tris-dipalladium) are unable to activate Rac1 or Pak1 in response to PDGF, and consequently, are unable to undergo PDGF-mediated cell migration. Furthermore, we also demonstrate that either chemical inhibition of MEK/ERK (U0126) or stable downregulation of PDGFRβ by shRNA similarly results in the loss of PDGF-induced ERK ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3649663 Mon, 07 Jun 2010 16:13:40 +0100 3649663 http://www.medworm.com/index.php?rid=3649664&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy825848861r41108%2F Abstract  Lim only protein (LMO) 4 acts as a transcriptional adapter and modulates mammary gland morphogenesis as well as breast oncogenesis in transgenic mice. Yet, the molecular and cellular mechanisms of these effects remain to be fully elucidated. Engrailed LMO4 fusion protein is a powerful dominant repressor of LMO4 activated transcription that was successfully used to discover the role of LMO4 as a transcriptional activator in mammary gland development in our previous studies using mouse models. In this manuscript, we investigated the cellular effects of LMO4 in human normal mammary epithelial cells (HMECs) and breast cancer cell lines using the Engrailed-LMO4 fusion protein. HMEC cell growth was inhibited by the expression of the Engrailed-LMO4 fusion protein. The de... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3649664 Mon, 07 Jun 2010 16:04:27 +0100 3649664 http://www.medworm.com/index.php?rid=3626793&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh8157272p4m3w132%2F Abstract  The paper presents diagnostic and therapeutic difficulties in two adolescents with widespread rhabdomyosarcoma (RMS) presenting with severe haemorrhages resulting from disseminated intravascular coagulation (DIC) and with laboratory features of acute tumour lysis syndrome (ATLS). Other published cases of childhood RMS with DIC at admission have been listed and reviewed. It has been concluded that the clinical picture of a widespread RMS in children may resemble acute hematologic malignancy and pose a big diagnostic problem. That is why the presence of small blue round cells morphologically similar to lymphoblasts and/or myeloblasts in bone marrow (BM), lacking hematopoietic makers, should prompt the pathologist to consider possible diagnosis of RMS. Inclusion of d... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3626793 Tue, 01 Jun 2010 15:42:56 +0100 3626793 http://www.medworm.com/index.php?rid=3626794&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg47g315634r3n358%2F This study indicates that consumption of soy foods may increase metastasis. Content Type Journal ArticleCategory Research PaperDOI 10.1007/s10585-010-9336-xAuthors Michelle M. Martínez-Montemayor, School of Medicine, Universidad Central del Caribe Department of Biochemistry and Cell Biology Bayamón PR USAElisa Otero-Franqui, School of Medicine, University of Puerto Rico Department of Biochemistry Medical Sciences Campus San Juan PR 00969 USAJoel Martinez, School of Medicine, Universidad Central del Caribe Department of Biochemistry and Cell Biology Bayamón PR USAAlina De La Mota-Peynado, School of Medicine, Universidad Central del Caribe Department of Biochemistry and Cell Biology Bayamón PR USALuis A. Cubano, School of Medicine, Universidad Central del Caribe Department of Bioc... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3626794 Tue, 01 Jun 2010 15:42:50 +0100 3626794 http://www.medworm.com/index.php?rid=3564829&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F07342246j3354313%2F This study evaluated the gender difference in multiple organ metastases in human small cell lung cancer (SBC-5) cells by using natural killer cell-depleted severe combined immunodeficient mice. Among multiple organ metastases, only bone metastasis formation significantly increased in female mice in comparison to males, while no significant difference was observed in the metastases to the liver and lungs. The suppression of androgen by castration or androgen receptor antagonist treatment in male mice also induced a significant increase of bone metastases. The number of osteoclasts in the bone metastatic lesions was greater in female mice and in mice with androgen suppression than in control male. However, there was no significant difference in the serum concentration of parathyroid ho... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3564829 Thu, 13 May 2010 07:45:27 +0100 3564829 http://www.medworm.com/index.php?rid=3561198&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2547001410363501%2F Abstract  The Ganoderma lucidum (Leyss. ex Fr.) Karst, an edible mushroom, has been utilized for centuries in East Asia to prevent or treat various diseases and to reduce the likelihood of cancer invasion and metastasis. The primary bioactive compounds are commonly considered to be polysaccharides and triterpenoids. Evidence that G. lucidum extract and its bioactive compounds may have a potential inhibitory effect on cancer invasion and metastasis is increasingly being reported in the scientific literature. This review assembles and summarizes past publications on the in vitro and in vivo effects of G. lucidum on cancer invasion and metastasis, and concludes that these effects occur through modulation of the phosphorylation of extracellular signal-regulated kinase (ERK1/2), ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3561198 Wed, 12 May 2010 07:47:11 +0100 3561198 http://www.medworm.com/index.php?rid=3546196&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl8xu208tq1453g73%2F This study examined the anti-metastatic effects of oxythiamine (OT) both in cell culture and in vivo. Cell culture results revealed that OT (0–20 μM) significantly inhibited the invasion and migration (IC50 = 8.75 μM) of Lewis lung carcinoma (LLC) cells. These effects of OT were accompanied by the inhibition of metalloproteinases-2 and -9 (MMP-2, MMP-9), urokinase-type plasminogen activator (uPA) activities and by the increases in protein expression of tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1, TIMP-2). We then implanted (s.c.) C57BL/6 mice with LLC cells and supplemented the mice with a low- or a high-dose of OT (250 or 500 mg/kg BW) daily for 5 wk. During the 5-wk period, OT supplementation decreased plasma MMP-2 activity in a dose-depende... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3546196 Fri, 07 May 2010 08:44:08 +0100 3546196 http://www.medworm.com/index.php?rid=3543720&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnl0u2732077wx471%2F Abstract  Bone likely provides a hospitable environment for cancer cells as suggested by their preferential localization to the skeleton. Previous work has shown that osteoblast-derived cytokines increased in the presence of metastatic breast cancer cells. Thus, we hypothesized that osteoblast-derived cytokines, in particular IL-6, MCP-1, and VEGF, would be localized to the bone metaphyses, an area to which breast cancer cells preferentially traffic. Human metastatic MDA-MB-231 breast cancer cells were inoculated into the left ventricle of the heart of athymic mice. Three to four weeks later, tumor localization within isolated femurs was examined using μCT and MRI. In addition, IL-6, MCP-1, and VEGF localization were assayed via immunohistochemistry. We found that MDA-MB-2... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3543720 Thu, 06 May 2010 09:03:27 +0100 3543720 http://www.medworm.com/index.php?rid=3539433&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa5g64610044r476q%2F Abstract  Metastatic bone disease caused by renal cell carcinoma (RCC) occurs frequently and becomes more and more prevalent presumably because survival times among patients with disseminated cancers are increasing. Patients with bone metastases from renal cell carcinoma suffer from severe pain, nerve compression syndromes and pathologic fractures. Very little is known about the mechanisms of skeletal metastases of RCC. Thus, to better understand the molecular mechanism of renal cell cancer (RCC) bone metastasis, it is crucial to develop new animal models. We have established a new animal model of RCC metastasis to bone by inoculation of human 786-O/luciferase cells into the left cardiac ventricle of athymic nude mice. The animals developed aggressive osteolytic bone destru... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3539433 Wed, 05 May 2010 08:13:36 +0100 3539433 http://www.medworm.com/index.php?rid=3468961&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwh867p327w31p06t%2F In this study, we examined the RANK/RANKL axis in OS cells, using a RANK-Fc protein to perturb this coupling in an effort to reduce OS cell growth. RANK-Fc suppressed OS cell migration (P < 0.005), invasion ability (P < 0.05), and anchorage-independent ability in collagen-1 gel (P < 0.005) following induction of anoikis and activation of caspase-3. OS cell proliferation was not perturbed by RANK-Fc. The anti-invasion and anti-metastasis capability of RANK-Fc is attributed to reduced extracellular signal-regulated protein kinase (ERK) signaling via RANK-Fc, though activation of NFκB, and altered expression of Akt, p38, JNK, and matrix metalloproteinase (MMP)-2 and -9 were ruled out. In vivo, activity of the RANK-Fc against OS cell migration and i... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3468961 Sat, 10 Apr 2010 07:48:20 +0100 3468961 http://www.medworm.com/index.php?rid=3468960&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6703825p8w276l0g%2F Abstract  Angiogenesis is a highly regulated physiological process that has been studied in considerable detail given its importance in several chronic pathologies. Many endogenous factors and hormones intervene in the regulation of angiogensis and classical as well as targeted drugs have been developed for its control. Angiogenesis inhibition has come off the bench and entered into clinical application for cancer therapy, particularly for metastatic disease. While the clinical benefit is currently in terms of months, preclinical data suggest that novel drugs and drug combinations could lead to substantial improvement. The many targets of endogenous angiogenesis inhibitors reflect the complexity of the process; in contrast, current clinical therapies mainly target the vascu... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3468960 Sat, 10 Apr 2010 07:48:20 +0100 3468960 http://www.medworm.com/index.php?rid=3450557&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw4742mt067047661%2F In this study, we examined the inhibitory effect of cationic liposome coupled with the murine endostatin gene (Lipo/mEndo) on growth of intraperitoneal disseminated colon cancer models. Intraperitoneal injection of Lipo/mEndo inhibited bioluminescent signals emitted from CT26 colon cancer cells stably expressing luciferase in the living mice and prolonged their survival times. Endostatin gene therapy suppressed the colony forming capability and VEGF concentration of ascites obtained from treated mice by 74 and 60%, respectively. When tested in a similar model using HCT116 human colon cancer cells, Lipo/mEndo and bevacizumab displayed comparable repressive effects on ascites formation and tumor foci dissemination on mesentery of experimental mice. Our results implicate that cationic l... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3450557 Wed, 07 Apr 2010 06:51:15 +0100 3450557 http://www.medworm.com/index.php?rid=3450556&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw447356144116716%2F Abstract  We studied the role of Neutrophil Gelatinase-associated Lipocalin (NGAL, lipocalin 2) in regulating the invasiveness of a cholangiocarcinoma cell line, RMCCA-1. RMCCA-1 cells expressed multiple forms of 25, 40, 75 and 115/135 kDa NGAL which were detected in the conditioned medium, whereas only the 25 kDa form was detected in the cell lysates. NGAL expression was induced by serum deprivation. NGAL downregulation by siRNA suppressed NGAL mRNA and protein expression by about 70–80%, concommittant with a significant reduction of in vitro invasiveness, migration and pro-MMP-9 activity, but not cell proliferation. Suppression of pro-MMP-9 activity paralleled a reduction of NGAL/MMP-9 complex in the conditioned medium, although MMP-9 mRNA expression was unaff... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3450556 Wed, 07 Apr 2010 06:51:15 +0100 3450556 http://www.medworm.com/index.php?rid=3450558&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr234065ju574tqr0%2F Abstract  To determine the feasibility and efficacy of stereotactic body radiotherapy (SBRT) for oligometastases from colorectal cancer (CRC). Total of 59 patients with 78 lesions confined to one organ and treated from 2001 to 2006 were involved in this retrospective review. These patients presented with 1–4 metastatic lesions of largest diameter of <7 cm, progressed after chemotherapy, and were amenable to local treatment. The median radiation dose administered was 42 Gy, which was delivered in 3 fractions. Lymph node lesions were most frequent, followed in order by the lung and liver. Five-year overall survival and local control rates were 29 and 19%, respectively. Cumulative gross tumor volume, site of metastasis, and SBRT dose were found to be significantl... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3450558 Tue, 06 Apr 2010 18:24:26 +0100 3450558 http://www.medworm.com/index.php?rid=3444845&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8046n70k102qr0m5%2F We describe a very sensitive assay for the highly reproducible detection and accurate quantification of human metastatic cells in mouse tissues and demonstrate its broad applicability to various experimental settings. Content Type Journal ArticleCategory Research PaperDOI 10.1007/s10585-010-9324-1Authors Anastasia Malek, Oncology Institute of Southern Switzerland Laboratory of Experimental Oncology 6500 Bellinzona SwitzerlandCarlo V. Catapano, Oncology Institute of Southern Switzerland Laboratory of Experimental Oncology 6500 Bellinzona SwitzerlandFrank Czubayko, Philipps-University, School of Medicine Department of Pharmacology and Toxicology Marburg GermanyAchim Aigner, Philipps-University, School of Medicine Department of Pharmacology and Toxicology Marburg Germany Journ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3444845 Sat, 03 Apr 2010 16:49:42 +0100 3444845 http://www.medworm.com/index.php?rid=3444846&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F901761661w4j2354%2F Abstract  To investigate the potential role of small breast epithelial mucin (SBEM) as a marker for detecting hematogenous micrometastasis in breast cancer and explore its clinical significance in neoadjuvant chemotherapy. SBEM protein expression in 82 tissue specimens of primary breast cancer was detected using immunohistochemistry (IHC), and SBEM expression in peripheral blood (PB) samples of 109 primary breast cancer patients (94 cases at stage I–III, 15 cases at stage IV) was detected by flow cytometry (FCM) and reverse transcription polymerase chain reaction (RT-PCR). Moreover, SBEM mRNA expression was monitored by quantification real-time PCR (QPCR) before and after 3 cycles’ neoadjuvant chemotherapy. SBEM expression correlated with tumor node metastasis (TNM) sta... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3444846 Sat, 03 Apr 2010 07:15:47 +0100 3444846 http://www.medworm.com/index.php?rid=3430398&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy2453673r74r4681%2F Abstract  Breast cancer is a complex disease resulting from a combination of genetic and environmental factors. Among environmental factors, body composition and intake of specific dietary components like total fat are associated with increased incidence of breast cancer and metastasis. We previously showed that mice fed a high-fat diet have shorter mammary cancer latency, increased tumor growth and more pulmonary metastases than mice fed a standard diet. Subsequent genetic analysis identified several modifiers of metastatic mammary cancer along with widespread interactions between cancer modifiers and dietary fat. To elucidate diet-dependent genetic modifiers of mammary cancer and metastasis risk, global gene expression profiles and copy number alterations from mammary can... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3430398 Wed, 31 Mar 2010 05:44:15 +0100 3430398 http://www.medworm.com/index.php?rid=3426128&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F026tt34032v45861%2F In this study, we examined the role of the interaction of carcinoma cells with laminin-5, which is a major component of submesothelial basement membranes and serves as a high-affinity ligand for α3β1 integrin, in carcinoma cell invasion. Human gastric carcinoma cell lines (MKN1, GT3TKB, and NUGC-4) adhered in an α3β1 integrin-dependent manner to the extracellular matrix deposited by peritoneal mesothelial cells. An in vitro invasion assay using the Boyden chamber system revealed that MKN1 cell migration through the membranes increased when the membranes were coated with matrices produced by mesothelial cells or with laminin-5-containing Matrigel as compared to Matrigel alone. The cell migration promoted by laminin-5-containing Matrigel was inhibited by the presence of anti-α3 in... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3426128 Tue, 30 Mar 2010 05:45:38 +0100 3426128 http://www.medworm.com/index.php?rid=3411933&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd383527236858388%2F Abstract  Activated α5β1 integrin occurs specifically on tumor cells and on endothelial cells of tumor-associated vasculature, and plays a key role in invasion and metastasis. The PHSCN peptide (Ac-PHSCN-NH2) preferentially binds activated α5β1, to block invasion in vitro, and inhibit growth, metastasis and tumor recurrence in preclinical models of prostate cancer. In Phase I clinical trial, systemic Ac-PHSCN-NH2 monotherapy was well tolerated, and metastatic disease progression was prevented for 4–14 months in one-third of treated patients. We have developed a significantly more potent derivative, the PHSCN-polylysine dendrimer (Ac-PHSCNGGK-MAP). Using in vitro invasion assays with naturally serum-free basement membranes, we observed that the PHSCN dendrimer was 1... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3411933 Fri, 26 Mar 2010 07:47:07 +0100 3411933 http://www.medworm.com/index.php?rid=3400447&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F46454x3q861x3783%2F Abstract  GPR56, a non-classical adhesion receptor, was previously reported to suppress tumor growth and metastasis in xenograft models using human melanoma cell lines. To understand whether GPR56 plays similar roles in the development of endogenous tumors, we analyzed cancer progression in Gpr56 −/− mice using a variety of transgenic cancer models. Our results showed that GPR56 suppressed prostate cancer progression in the TRAMP model on a mixed genetic background, similar to its roles in progression of melanoma xenografts. However, its roles in other cancer types appeared to be complex. It had marginal effects on tumor onset of mammary tumors in the MMTV–PyMT model, but had no effects on subsequent tumor progression in either the MMTV–PyMT mice or the melanoma mod... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3400447 Tue, 23 Mar 2010 18:05:26 +0100 3400447 http://www.medworm.com/index.php?rid=3366962&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy747617vt588jkp6%2F Abstract  Despite the potentially crucial contributions of the omentum in the regulation of ovarian cancer metastatic growth, it remains a poorly understood organ. Due to its anatomic location and structural fragility, the omentum presents inherent challenges to mechanism-based in vivo studies. Thus, the availability of an ex vivo omental model would, in part, address some of these difficulties posed. Here we describe a technique for identifying, isolating and maintaining ex vivo cultures of omenta from immune-compromised and -competent mice. Ex vivo culture conditions were developed that maintain tissue viability, architecture, and function for up to 10 days. Further experiments demonstrate that the ex vivo culture conditions allow for the proliferation of ovarian can... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3366962 Sun, 14 Mar 2010 11:27:03 +0100 3366962 http://www.medworm.com/index.php?rid=3366963&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx50231172tkj1l85%2F Abstract  CXCL12/CXCR4 signaling, being important in the homing of cancer cells to lungs, bone and other organs, is a promising therapeutic target. Our purpose was to determine whether a peptide-based antagonist of CXCR4 would reduce primary tumor growth and/or metastasis in a preclinical mouse model of inflammatory breast cancer. We improved an existing model of inflammatory breast cancer for this study by luciferase transfection of SUM149 cells and the monitoring of such cells in mice by imaging and the luciferase assay. We implanted 2 × 106 SUM49-Luc cells along with matrigel into the left thoracic mammary fat pad of nude mice to produce tumors. Our mouse model exhibited important features of inflammatory breast cancer, namely, aggressive local disease, local m... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3366963 Sun, 14 Mar 2010 11:27:02 +0100 3366963 http://www.medworm.com/index.php?rid=3363235&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9246322788r2hg52%2F Abstract  Advanced metastatic disease is difficult to manage and specific therapeutic targets are rare. We showed earlier that metastatic breast cancer cells use the activated conformer of adhesion receptor integrin αvβ3 for dissemination. We now investigated if targeting this form of the receptor can impact advanced metastatic disease, and we analyzed the mechanisms involved. Treatment of advanced multi-organ metastasis in SCID mice with patient-derived scFv antibodies specific for activated integrin αvβ3 caused stagnation and regression of metastatic growth. The antibodies specifically localized to tumor lesions in vivo and inhibited αvβ3 ligand binding at nanomolar levels in vitro. At the cellular level, the scFs associated rapidly with high affinity αvβ3 and dis... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3363235 Fri, 12 Mar 2010 06:50:52 +0100 3363235 http://www.medworm.com/index.php?rid=3360372&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd28l582m5888hg54%2F Abstract  Lung cancer is the leading cause of cancer death in men and women worldwide. Since the occurrence of metastases in distant organs is the major reason for mortality of cancer patients, we need to elucidate the underlying mechanisms. Many studies featuring analysis of gene expression, comparative genomic hybridization and loss of heterozygosity analysis have been performed and generated support for the hypothesis that metastatic potential is acquired early in tumorigenesis. Furthermore, it is now clear that the majority of tumor cells have the potential to metastasize. Although many changes in gene expression profiles have been established retrospectively, translational research is now a high priority to enable clinical application and treatment based on laboratory ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3360372 Thu, 11 Mar 2010 18:17:45 +0100 3360372 http://www.medworm.com/index.php?rid=3355582&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa45487u783816746%2F In conclusion, we have developed a novel surgical adjuvant model of metastatic OS in immunocompetent mice that closely recapitulates the clinical situation, allowing the evaluation of novel therapeutics in the context of minimal residual disease. Content Type Journal ArticleCategory Research PaperDOI 10.1007/s10585-010-9318-zAuthors Joseph L. Sottnik, Colorado State University Animal Cancer Center, Department of Clinical Sciences Fort Collins CO 80523 USADawn L. Duval, Colorado State University Animal Cancer Center, Department of Clinical Sciences Fort Collins CO 80523 USAE. J. Ehrhart, Colorado State University Animal Cancer Center, Department of Clinical Sciences Fort Collins CO 80523 USADouglas H. Thamm, Colorado State University Animal Cancer Center, Department of Clinical Sci... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3355582 Wed, 10 Mar 2010 15:31:01 +0100 3355582 http://www.medworm.com/index.php?rid=3355583&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2367631u4767u831%2F Abstract  The present study investigated the intracellular regulation of E-cadherin in ovarian carcinoma. E-cadherin expression and regulation by Snail and Pak1 were studied in ES-2 and OVCAR-3 ovarian cancer cells in vitro. Twist1, Zeb1 and Vimentin mRNA expression and HIF-1α protein expression were analyzed in 80 and 189 clinical specimens, respectively. OVCAR-3 cells incubated with an anti-E-cadherin antibody formed smaller and looser spheroids compared to controls. Snail silencing using Small Hairpin RNA in ES-2 cells reduced invasion and MMP-2 activity, with unaltered cellular morphology. Using dominant negative (DN) and constitutively active (CA) Pak1 constructs, we found that DN Pak1 ES-2 and OVCAR-3 clones had reduced attachment to matrix proteins, invasion and MMP-... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3355583 Wed, 10 Mar 2010 15:31:00 +0100 3355583 http://www.medworm.com/index.php?rid=3323732&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frv6t25r0n6215l36%2F Abstract  The aim of this study was to assess the intratumoral and peritumoral distribution of lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) in colorectal cancer and their relationships with patients’ clinicopathological characteristics and survival. Paraffin sections of 81 primary colorectal cancers were examined by immunohistochemical staining using monoclonal antibody D2-40. Peritumoral LVD was significantly higher than intratumoral LVD (P = 0.000). Both intratumoral LVD and peritumoral LVD were correlated with the presence of LVI (P = 0.006 and P = 0.003, respectively). LVI, intratumoral LVI and peritumoral LVI were identified, respectively in 38, 28 and 32% of the samples investigated. Both intratumoral LVI and peritum... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3323732 Mon, 01 Mar 2010 18:10:01 +0100 3323732 http://www.medworm.com/index.php?rid=3312736&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flu0305w765w34612%2F Abstract  Data from animal studies indicate that platelets play a key role in tumor dissemination and metastasis. We therefore hypothesized that metastastic cancer patients may display a specific platelet phenotype. Percentage of activated, p-selectin positive platelets as well as platelet contents (i.e., plasma and platelet count-corrected serum levels of VEGF-A, CXCL12, CXCL4, and thrombospondin-1) were analyzed in 43 patients with newly diagnosed metastatic disease prior to treatment. Tumor patients had increased platelet counts and significantly elevated percentages of activated platelets. Moreover, the platelet content of VEGF-A in cancer patients was significantly increased compared to healthy controls, while thrombospondin-1, CXCL12 and CXCL4 were significantly decrea... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3312736 Thu, 25 Feb 2010 06:55:43 +0100 3312736 http://www.medworm.com/index.php?rid=3308103&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwl8n14661q995432%2F Abstract  A large-scale gene expression study of melanoma metastases was performed to identify genes involved in late-stage tumor progression. Overall 248 genes, out of more than 47,000 tested, are differentially expressed when comparing peripheral areas (invasion front) with central tumor areas of melanoma metastases. As determined by gene ontology analysis, members of the STAT signaling pathway show significant enrichment. In particular, Stat1 is highly expressed in peripheral compared with central tumor areas. In line with this, stable knockdown of STAT1 in metastatic melanoma cells significantly impairs their migratory and invasive capacity in wounding and matrigel assays. Moreover, STAT1 knockdown affects the metastatic behavior of melanoma cells in a mouse model of mel... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3308103 Wed, 24 Feb 2010 06:58:17 +0100 3308103 http://www.medworm.com/index.php?rid=3308102&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw30058r37t7164x4%2F In this study, we examined FAK and phosphorylated FAK Tyr397 expression in a large series of HCCs. We found that both FAK and phosphorylated FAK Tyr397 were overexpressed in HCC samples and HCC cell lines. Increased FAK and phosphorylated FAK Tyr397 expressions were correlated with tumor stage, vascular invasion and intrahepatic metastasis in HCC. Furthermore, HCC cell adhesion, migration and invasion were substantially impaired by siRNA-mediated knockdown of FAK expression, whereas cell growth, apoptosis and cell cycle distribution were not affected. In addition, depletion of FAK induced a significant reduction in expressions and activities of both MMP-2 and MMP-9. Taken together, FAK contributes to invasion and metastasis of HCC partly through regulating expressions and activations... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3308102 Wed, 24 Feb 2010 06:58:17 +0100 3308102 http://www.medworm.com/index.php?rid=3303647&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk075425j67041165%2F Abstract  It was expected that with the advent of genomics, oncology may defeat the deadliest forms of cancer including malignant melanoma, but the past years have indicated that this is not the case. Despite the stunning success of genomics in defining markers or gene signatures for breast cancer prognosis and predicting therapies, there is virtually no progression in malignant melanoma. This is happening when experimental oncology or metastasis research is using several rodent and human melanoma models, when our knowledge on the metastatic cascade is actually derived from these models. Our critical analysis of these studies revealed several factors which might be responsible for this failure. First, it is evident, that these studies must be based on rigorous sample collec... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3303647 Tue, 23 Feb 2010 07:48:07 +0100 3303647 http://www.medworm.com/index.php?rid=3295546&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F40v524h453935454%2F Abstract  Angiosarcomas are high-grade vascular tumors associated with poor prognosis due to their aggressive nature. Occasional skeletal manifestations present commonly as osteolytic destruction. The 55-years-old patient presented in this case report had a disease-free 4 years interval between splenectomy after primary angiosarcoma of the spleen and an unusual skeletal metastatic pattern mimicking benign angiomatosis. Despite lacking radiographic evidence for a highly aggressive osseous process, the histopathological resemblance of the bone biopsy with the primary tumor manifestation and the fulminant course of disease after onset of disseminated osseous spread confirmed the malignant character of the vascular tumor. The case demonstrates the highly variable radiograph... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3295546 Sat, 20 Feb 2010 06:53:08 +0100 3295546 http://www.medworm.com/index.php?rid=3270398&cid=s_33451_6_f&fid=33451&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0672p8r005252467%2F Abstract  Metastasis virulence, a significant contributor to breast cancer prognosis, is influenced by environmental factors like diet. We previously demonstrated in an F2 mouse population generated from a cross between the M16i polygenic obese and MMTV-PyMT mammary cancer models that high fat diet (HFD) decreases mammary cancer latency and increases pulmonary metastases compared to a matched control diet (MCD). Genetic analysis detected eight modifier loci for pulmonary metastasis, and diet significantly interacted with all eight loci. Here, gene expression microarray analysis was performed on mammary cancers from these mice. Despite the substantial dietary impact on metastasis and its interaction with metastasis modifiers, HFD significantly altered the expression of only ... Clinical and Experimental Metastasis journals http://www.medworm.com/rss/comments.php?id=3270398 Fri, 12 Feb 2010 07:10:19 +0100 3270398