CONSTITUTIVE EXPRESSION OF MULTIPLE GROWTH-FACTOR GENES BY MELANOMA-CELLS BUT NOT NORMAL MELANOCYTES

In a panel of metastatic melanoma cell lines we found steady-state mRNA transcripts for multiple growth factors including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A, PDGF-B, transforming growth factor (TGF)-beta-1, TGF-alpha, melanoma growth-stimulating activity (MGSA), interleukin (IL)-1-alpha, and IL-1-beta but not insulin-like growth factor (IGF)-1 or IGF-2. Expression of growth factor genes was constitutive because prior to RNA extraction melanoma cells were maintained in a chemically defined culture medium free of exogenous growth factors. Each of four cell lines had an individual pattern of expression of either two, four, five, or seven growth factors; however, all cell lines shared expression of the bFGF gene. Two strains of normal melanocytes expressed TGF-beta-1 but not bFGF, PDGF, TGF-alpha, or MGSA mRNA at detectable levels. We tested growth-modulatory effects of the growth factors most frequently expressed by melanoma cells (bFGF, TGF-alpha, TGF-beta, PDGF). None of these stimulated melanoma cell growth consistently, whereas exogenous, acid-activated TGF-beta inhibited melanoma growth at concentrations > 10 ng/ml, suggesting that bioactive TGF-beta may represent a physiologic growth inhibitor. Neither neutralizing antisera to PDGF or TGF-alpha nor a monoclonal antibody to the epidermal growth factor (EGF)-receptor inhibited melanoma cell growth. Our results indicate that multiple growth factors are expressed simultaneously and constitutively by melanoma cells but not normal melanocytes in culture. Expression of bFGF is a common feature underscoring the significance of bFGF as an autocrine factor for melanoma cells as described earlier. Secreted PDGF and TGF-alpha are apparently not involved in or not essential for autocrine growth stimulation of melanoma cells.