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Mercy Kibe, Jordan J Toutounchian, Ryan Yates, Jena J Steinle, Matthew W Wilson, Vanessa Marie Morales; Identification of a Small Cohort of Genes That Might Drive Metastases in Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6442.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma (UM) remains the most common primary intraocular cancer in adults. It metastasizes mainly to the liver in 50% of patients who develop this cancer. The mechanisms that govern hematogenous spread to the liver in UM remain unclear which underlines the urgency for continued research in this field. In this study, we investigated the differences in gene expression in primary and metastatic uveal melanoma cell lines using a PCR array limited to a small cohort of 84 genes to evaluate the expression of genes associated with extracellular matrix, adhesion, and metastatic pathways. We hypothesized genes associated with adhesion and attachment to the extracellular matrix as well as metastasis would be highly expressed in the metastatic cell line relative to the primary tumor cell line.
Targeted PCR arrays were used to evaluate gene expression of metastasis- and extracellular matrix and cell adhesion-associated genes using the primary UM cell lines Mel 270 and 92.1 and the metastatic UM cell line OMM 2.5.
Gene analysis was expressed as the relative gene upregulation or downregulation of metastatic to primary UM. We found differences in gene expression among the different cells lines. Results were clustered into genes involved in the invasion of the basement membrane, adhesion molecules, and immunosuppressive factors. Within the differentially regulated genes we identified a small cohort of genes that might drive metastases. Among the genes, we observed fold upregulation in TNC, NCAM1 and COL4A2. We also identified genes from the ITGA family, the MMP inhibitor TIMP3, VEGFA, and the oncogene SRC to be upregulated in metastatic over primary UM. However, genes associated with suppression of metastases such as CDH1, the metastasis suppressor KISS1, and TNFSF10, showed a reduction in gene expression in metastatic relative to primary cell lines.
Our work identified a series of genes that might drive metastases. Ongoing work aims at analyzing further differences among primary UM that becomes metastatic at the genetic and protein levels. Further in vivo experiments will test these differences in the presence of the tumor microenvironment. experiments will test these differences in the presence of the tumor microenvironment.
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