Stimulation and Inhibition of Uveal Melanoma Invasion by HGF, GRO, IL-1α and TGF-β

PURPOSE. To investigate potential factors involved in uveal melanoma migration and invasion in vitro. METHODS. Using a microchemotaxis chamber, the effects were studied of a range of stimulators and inhibitors on a series of 10 primary uveal melanomas and 2 uveal melanoma cell lines, by assessing invasion through an 8-μm pore membrane, precoated with an extracellular matrix solution. In addition, invasion in response to the effect of cells and conditioned media derived from the liver and other tissues was studied for one uveal melanoma culture, by using double-chambered wells, and invasion was assessed through an 8-μm pore membrane, precoated with synthetic extracellular matrix. In all instances, invading cells were counted under X 400 magnification on the lower surface of the membrane. Levels of invasion were correlated with histopathologic markers of prognosis. RESULTS. Conditioned media and cells derived from other tissues, including the liver, increased cellular invasion of the uveal melanoma cell line studied. For specific regulators, maximum stimulation of invasion was induced by hepatic growth factor (HGF), growth-related oncogene (GRO), and macrophage inflammatory protein (MIP)-1β, whereas significant inhibition was induced by IL-1α, TGF-β1, and TGF-β2. CONCLUSIONS. The primary site of metastasis in 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 adhesion, migration, invasion, and proliferation of tumor cells. HGF, GRO, MIP-1β, IL-1α TGF-β1, and TGF-β2 may play a significant role in regulating invasion of uveal melanoma cells.