HUMAN-MELANOMA CELLS EXPRESS FUNCTIONAL ENDOTHELIN-1 RECEPTORS

Current evidence suggests that endothelium-derived factors enhance hum an melanoma vascular invasion. Therefore, we studied human melanoma ce ll expression of receptors to the endothelium-derived peptide, endothe lin-1 (ET-1), and determined if they respond to ET-1 with proliferatio n and chemokinesis. Human metastatic melanoma cell lines were found to have specific, saturable, high affinity ET-1 binding. Northern analys is and competitive inhibition studies confirmed that melanoma cells ex press the ET(B) receptor isoform. Ten nanomolar ET-1 caused an 8.2 to 25.5-fold increase in intracellular free calcium. ET-1 was found to be a weak mitogen for melanoma cells, however, melanoma cell chemokinesi s was significantly increased by ET-1. These data suggest that ET-1 ma y be involved in providing a chemokinetic and growth factor environmen t that enhances perivascular proliferation and invasiveness of melanom a cells. (C) 1994 Academic Press, Inc.