Role of epidermal growth factor receptor in the metastasis of intraocular melanomas.
OBJECTIVE
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.
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Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Niederkorn
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D066246:ErbB Receptors / Q000276:immunology / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D008545:Melanoma / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014604:Uveal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D066246:ErbB Receptors