Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR

The expression patterns of vascular endothelial growth factor (VEGF) and it s two receptors, flt-1 and KDR, were assessed in normal human melanocytes, transformed melanocytes expressing the simian virus 40 Tgene (SV40T), and m elanoma cells derived from primary and metastatic lesions. Constitutive exp ression of VEGF, flt-1, and KDR mRNA and proteins was observed in the major ity of primary and metastatic melanoma cell lines, and in SV40T-transformed melanocytes. VEGF expression in melanoma cell lines was further enhanced b y exogenous growth factors including insulin and fetal calf serum. By contr ast, neonatal melanocytes did not express VEGF or VEGF receptors and VEGF e xpression could not be induced by exogenous growth factors. Exogenous VEGF had no significant effects on melanoma cell proliferation or on production of a transcriptional target for VEGF, urokinase-type plasminogen activator. Down-regulation of VEGF expression in the metastatic melanoma cell line WM 164 through transfection of a VEGF antisense construct similarly did not af fect proliferation of the transfected cells in the presence or absence of e xogenous VEGF. In summary, coexpression of VEGF and its receptors is a tumo r-associated phenomenon in melanoma development. However VEGF production do es not support autocrine proliferation of the melanoma cell lines tested.