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IG Rennie, JK L Baker, SR Elshaw, AK Murray, CE Nichols, K Sisley; HGF, GRO and MIP-1ß Stimulate Uveal Melanoma Migration Whilst IL-1 and TGF-ß Inhibit Migration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1123.
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Purpose: To investigate potential factors involved in uveal melanoma migration and invasion in vitro. Methods: After enucleation, uveal melanoma biopsies were collected from theatre and grown as short-term cultures. Using a micro-chemotaxis chamber, the effects of a range of stimulators and inhibitors were studied on a series of ten primary uveal melanomas and two uveal melanoma cell lines. Migration and invasion were assessed through an 8µM pore membrane, pre-coated with an extra cellular matrix solution and invaded cells were counted under x400 magnification on the lower surface on the membrane. Levels of invasion were correlated with histo-pathological markers of prognosis. Results: HGF stimulated significant increases in invasion and migration of all primary tumours and cell lines, whilst eleven of the twelve cultures significantly responded to GRO and MIP-1ß . Most cultures studied with the exception of two were inhibited by both TGF-ß isoforms, and all were inhibited by IL-1α. Conclusions: The primary site of metastasis for patients with uveal melanoma is the liver. For the degree of site-specificity commonly seen, regulators involved in the process may be expressed at the secondary sites, promoting tumour cell adhesion, migration, invasion and proliferation. HGF, GRO, MIP-1ß, IL-1α, TGF-ß1 and TGF-ß2 may play a significant role in regulating uveal melanoma invasion. Supported by Yorkshire Cancer Research, National Eye Research Council and the Humane Research Trust.
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