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Invasive Activity (invasive + activity)
Selected AbstractsNm23-H1 expression of metastatic tumors in the lymph nodes is a prognostic indicator of oral squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Yi-Fen Wang Abstract We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens. © 2007 Wiley-Liss, Inc. [source] Pathology of soft-tissue tumors: Daily diagnosis, molecular cytogenetics and experimental approachPATHOLOGY INTERNATIONAL, Issue 8 2009Hiroshi Iwasaki This article reviews problems in diagnostic pathology and molecular cytogenetics of soft-tissue tumors. Also discussed are the origin of soft-tissue sarcomas and the molecular basis of effective target therapy for sarcomas. Molecular cytogenetic analysis of tumor-specific chromosomal translocations and associated fusion gene transcripts offers a useful adjunct to the diagnosis of soft-tissue tumors, but recent studies have indicated a growing number of fusion gene variations in each tumor type. In pleomorphic sarcoma/malignant fibrous histiocytoma, the alternative lengthening of telomeres (ALT) mechanism may result in formation of anaphase bridges and marked nuclear pleomorphism. The histogenesis of soft-tissue sarcomas has been a matter of controversy. In the present experimental model using s.c. injection of 3-methylcholanthrene in C57BL/6 mice pretreated with bone marrow-transplantation from green fluorescent protein (GFP)-positive green mice, the bone marrow-derived mesenchymal stem cells as well as the tissue-resident mesenchymal cells in the peripheral soft tissues are possible originators of sarcomagenesis. Little is known about a molecular basis of target therapy for sarcomas. Platelet-derived growth factor-BB (PDGF-BB) enhances the invasive activity of malignant peripheral nerve sheath tumor (MPNST) cells through platelet-derived growth factor receptor (PDGFR) phosphorylation, whereas imatinib mesylate inhibited such activity, suggesting that targeting PDGFR-, may result in the establishment of novel treatment for MPNST. In addition, emmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMP), playing a crucial role in tumor progression, invasion and metastasis. The MMP upregulation mechanism mediated by tumor-associated emmprin may be a potentially useful target in anti-tumor invasion therapy for sarcomas. [source] Wilms tumor gene protein 1 is associated with ovarian cancer metastasis and modulates cell invasionCANCER, Issue 7 2008Maria V. Barbolina PhD Abstract BACKGROUND Although metastatic disease is the primary cause of death from epithelial ovarian carcinoma, to the authors' knowledge the cellular mechanisms that regulate intraperitoneal metastasis are largely unknown. Metastasizing ovarian carcinoma cells encounter a collagen-rich microenvironment because the submesothelial matrix is comprised mainly of interstitial collagens Types I and III. METHODS Immunohistochemistry using primary and metastatic ovarian carcinoma samples was employed to detect expression of Wilms tumor gene protein 1 (WT1). Three-dimensional (3D) collagen culture, real-time reverse transcriptase-polymerase chain reaction, and immunofluorescent staining were used to evaluate changes in WT1 RNA and protein expression in response to 3D collagen culture. Boyden chamber invasion assay, scratch-wound motility assay, and Western blot analysis were used to establish the function of WT1 in ovarian carcinoma cells. RESULTS To model intraperitoneal invasion in vitro, ovarian cancer cells were cultured in a 3D collagen microenvironment. 3D collagen culture resulted in robust induction of WT1 at the mRNA and protein levels. WT1 expression was prevalent in primary ovarian tumors and was retained in paired peritoneal metastases. Functional studies supported a role for WT1 in intraperitoneal invasion, because siRNA knockdown of WT1 expression reduced the ability of ovarian cancer cells to invade 3D collagen gels. CONCLUSIONS The data from the current study identify a novel regulatory mechanism for the control of WT1 expression and provide evidence for a functional role of WT1 protein in the control of cellular invasive activity. Cancer 2008. ©2008 American Cancer Society. [source] Simvastatin inactivates ,1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cellsCANCER SCIENCE, Issue 6 2007Ikuko Takeda The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, also called statins, are commonly used as lipid-lowering drugs that inhibit cholesterol biosynthesis. An anticancer effect, as a pleiotropic function of certain statins, has been hypothesized. In the present study, we investigated the effect of simvastatin, one of the natural statins, on cell proliferation, cell cycle, invasive activity, and molecular expressions associated with cell,extracellular matrix adhesion, signal transduction, and DNA synthesis in Tu167 and JMAR cells from head and neck squamous cell carcinoma. The addition of simvastatin resulted in a dose-dependent inhibition of cell growth and migration into the extracellular matrix. Considerable morphological changes occurred after treatment with simvastatin, demonstrating loss of cell adhesion and disruption of actin filaments in cytoplasm. The inhibitory effect of simvastatin on cell proliferation seemed to be associated with cell cycle arrest and increased expression of p21, p27, and activated caspase-3. The expression of ,1-integrin, a counter adhesion for the extracellular matrix, phosphorylated FAK, and phosphorylated ERK was decreased by treatment with simvastatin. The proapoptotic effect of simvastatin was inhibited by treatment with mevalonate. cDNA microarray assay demonstrated that molecular changes resulting from treatment with simvastatin included the up-regulation of cell cycle regulators and apoptosis-inducing factors and the down-regulation of integrin-associated molecules and cell proliferation markers. Of down-regulated genes induced by simvastatin treatment, a significant depletion of thymidylate synthase was confirmed using western blot analysis. These results imply that simvastatin has the potential to be effective for the prevention of the growth and metastasis of cancer cells. (Cancer Sci 2007; 98: 890,899) [source] | ||||||||||