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J.-L. Yang, A. Jayagopal, M. S. Chang; Reduction of Aggressive Behavior in Uveal Melanoma Cells with Increased Bves Expression. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5778.
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© ARVO (1962-2015); The Authors (2016-present)
An important prognostic indicator in uveal melanoma (UM) is epithelial vs. spindle morphology. We have previously reported that Bves (blood vessel epicardial substance), a novel adhesion molecule, plays a role in modulating epithelial- mesenchymal phenotype in corneal epithelial cells. These observations led to our hypothesis that alterations in Bves expression will alter UM cell morphology and behavior.
Two human UM cell lines, OM43 (primary UM) and OMM 2.3 (liver metastatic UM) were stably transfected with an expression construct encoding Bves-green fluorescent protein (GFP) fusion protein. The Bves-GFP overexpressing cells and parental cells were evaluated for cell growth characteristics (colony formation assay, MTT cell proliferation assay), cell motility and invasiveness (wound healing assay, Boyden chamber assays, cell attachment), and cell morphology. In addition, Western blot and immuno-staining studies were performed to exanimate alterations in cytoskeleton and adhesion junction formation.
UM cells stably overexpressing Bves-GFP (OM431-cwg and OMM2.3-cwg) exhibit significant changes in cellular behavior compared to untransfected parental UM cells. OM431-cwg and OMM2.3-cwg cells exhibit 30-50% decrease in cell motility, invasion, and proliferation compared to their respective untransfected parental UM cells. Cellular attachment efficiency is increased with overexpression of Bves in both cell lines. Western blotting, OM431-cwg and OMM2.3-cwg cells exhibit increased E-cadherin, an important transmembrane component of adherens junction, in OMM2.3-cwg cells. Over-express Bves also induced increased number of cells exhibiting spindle morphology.
Over-expression of Bves in primary and metastatic uveal melanoma cells leads to change in cell behavior that may be considered to be less aggressive. Furthermore, over-expression of Bves is also associated with increase spindle morphology. Potential molecular mechanisms for these observation my be through Bves regulatory effects on cell-cell contact formation as indicated by increased levels of E-cadherin.
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