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 greater than 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.
Rodeck
U
U
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Melber
K
K
Kath
R
R
Menssen
H D
HD
Varello
M
M
Atkinson
B
B
Herlyn
M
M
D015152:Blotting, Northern; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D015291:Transforming Growth Factors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D015291:Transforming Growth Factors; D066246:ErbB Receptors