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Role of epidermal growth factor receptor in the metastasis of intraocular melanomas
1Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Purpose:
To explore the expression and function of epidermal growth factor receptor (EGFR) expression on human uveal melanoma cells.
Methods:
Five human uveal melanoma cell lines were examined by flow cytometry for the expression of EGFR. The correlation between EGFR expression and metastasis of uveal melanoma cells was tested in a nude mouse model of intraocular melanoma. The effect of EGFR on liver homing of blood-borne uveal melanoma cells was tested by tracing the fate of radiolabeled cells treated with anti-EGFR monoclonal antibody. The capacity of EGFR to inhibit the cytotoxic effects of tumor necrosis factor-alpha (TNF-alpha) was determined in vitro. The role of EGFR in promoting metastatic disease was studied by infusing intraocular melanoma-bearing mice using a neutralizing antibody against EGFR.
Results:
EGFR was expressed to varying degrees on all eight human uveal melanoma cell lines. Expression of EGFR correlated with metastatic potential and capacity of blood-borne uveal melanoma cells to localize in the liver. EGFR rendered uveal melanoma cells resistant to the cytolytic effects of TNF-alpha. Blocking EGFR with a neutralizing monoclonal antibody increased the susceptibility of uveal melanoma cells to TNF-mediated cytolysis, inhibited metastases, and prolonged host survival.
Conclusions:
The expression of EGFR on five human uveal melanoma cell lines is correlated with an increased capacity to localize in the liver, an increased resistance to TNF-mediated lysis, and decreased survival. Targeting EGFR expression and function may be a fruitful strategy for managing patients with uveal melanoma.