ROLE OF EPIDERMAL GROWTH-FACTOR RECEPTOR IN THE METASTASIS OF INTRAOCULAR MELANOMAS

PURPOSE. To explore the expression and function of epidermal growth fa ctor receptor (EGFR) expression on human uveal melanoma cells. METHODS . Five human uveal melanoma cell lines were examined by now cytometry for the expression of EGFR. The correlation between EGFR expression an d metastasis of uveal melanoma cells was tested in a nude mouse model of intraocular melanoma. The effect of EGFR on Liver homing of blood-b orne uveal melanoma cells was tested by tracing the fate of radiolabel ed cells treated with anti-EGFR monoclonal antibody. The capacity of E GFR to inhibit the cytotoxic effects of tumor necrosis factor-alpha (T NF-alpha) was determined in vitro. The role of EGFR in promoting metas tatic disease was studied by infusing intraocular melanoma-bearing mic e using a neutralizing antibody against EGFR. RESULTS. EGFR was expres sed to varying degrees on all eight human uveal melanoma cell lines. E xpression of EGFR correlated with metastatic potential and capacity of blood-borne uveal melanoma cells to localize in the liver. EGFR rende red uveal melanoma cells resistant to the cytolytic effects of TNF-alp ha. Blocking EGFR with a neutralizing monoclonal antibody increased th e susceptibility of uveal melanoma cells to TNF-mediated cytolysis, in hibited metastases, and prolonged host survival. CONCLUSIONS. The expr ession of EGFR on five human uveal melanoma cell lines is correlated w ith an increased capacity to localize in the liver, an increased resis tance to TNF-mediated lysis, and decreased survival. Targeting EGFR ex pression and function may be a fruitful strategy for managing patients with uveal melanoma.