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I.G. Rennie, J.K. L. Woodward, K. Sisley; TGFß Plays Both a Stimulatory and Inhibitory Role in the Regulation of Uveal Melanoma Invasion in vitro . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3420.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: TGFß has been shown to mainly inhibit Uveal melanoma invasion, but the mechanism of this regulation is not known. The aim of this study was to explore the effect of TGFß stimulation on the adhesive interactions of uveal melanomas with the extra cellular matrix (ECM) and endothelium and secretion of collagenases. Methods: The adhesion of invasive and non–invasive uveal melanoma cell lines to ECM and endothelial cells, and degradation of the ECM was assessed following modulation by TGFß. In addition changes in cell adhesion molecule expression were assessed by flow cytometry and conditioned medium was analysed by gelatin zymography. Results: Treatment by TGFß increased levels of adhesion molecule and latent MMP–2 expression, and also adhesion to hepatic endothelial cells by non–invasive cells. Conversely TGFß reduced adhesion to laminin and a laminin–binding integrin by invasive cells but have no effect on their adhesion to the endothelium. Conclusions: Findings suggest that TGFß has a dual role in controlling uveal melanoma progression. Early stage non–invasive melanomas appear to be inhibited by TGFß, whereas the invasive propensities of advanced uveal melanomas could be enhanced.
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