Up-regulation of ephrin-A1 during melanoma progression

Ephrin-A1, formerly called B61, is a new melanoma growth factor; it is angi ogenic and chemoattractant for endothelial cells. EPH-A2, or ECK (a recepto r for ephrin-A1), is ectopically expressed in most melanoma cell lines; the pathology where this expression is first manifested and the possible role of the receptor in tumor progression are unknown. To determine these, we st udied the expression of this ligand and receptor in biopsies of benign and malignant melanocytic lesions. EPH-A2 was not detected in normal melanocyte s, benign compound nevi or advanced melanomas, though it was found in 2 of 9 biopsies of malignant melanoma in situ. Ephrin-A1 was present in occasion al early lesions and in advanced primary melanomas (43%) and metastatic mel anomas (67%). Expression of ephrin-A1 was induced in melanoma cells by pro- inflammatory cytokines. Our findings are consistent with 2 possible roles f or ephrin-A1 in melanoma development: it may promote melanocytic cell growt h or survival and induce vascularization in advanced melanomas. Both effect s may be potentiated by inflammatory responses. Our data are consistent wit h earlier observations that an inflammatory infiltrate is associated with p oor prognosis in thin primary melanomas. Int. J. Cancer (Pred. Oncol.) 84:4 94-501, 1999. (C) 1999 Wiley-Liss, Inc.