Editor’s statement In this manuscript Dr. Ruth Halaban and her collaborators demonstrate the mitogenic action on melanocytes of a known growth factor synergistically with cAMP, which has not been demonstrated so far. In addition, the data demonstrate that mitogenic activity toward normal melanocytes in tissue extracts and melanoma cells is antigenically related to bFGF, suggesting the involvement of this growth factor in the transformation of normal melanocytes to melanomas.
Summary
Normal human melanocytes, unlike pigment cells from metastatic melanomas, do not survive in culture in routine, serum-supplemented media. The search for natural growth factors for melanocytes has shown that mitogenic activity is ubiquitous in several tissues and in melanomas. Of several known growth factors tested, basic fibroblast growth factor (bFGF) was the only one mitogenic for melanocytes but only in the presence of cyclic-adenosine-monophosphate (cAMP) stimulators. The mitogenic activity toward melanocytes in tissues and melanoma cell extracts had high affinity for heparin and antibodies to bFGF synthetic peptides. These results suggest that one of the growth factors for melanocytes might be bFGF or a bFGF-like polypeptide and that autocrine production of bFGF-like molecules by melanoma cells may contribute to the malignant phenotype of melanocytes. Because acidic FGF (aFGF) did not stimulate growth, the receptors for bFGF on melanocytes might be significantly different from those for a FGF.
References
Abraham, J. A.; Mergia, A.; Whang, J. L.; Tumolo, A.; Friedman, J.; Hjerrild, K. A.; Gospodarowicz, D.; Fiddes, J. C. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science 233: 545–548; 1986.
Baird, A.; Esch, F.; Gospodarowicz, D.; Guillemin, R. Retina-and eye-derived endothelial cell growth factors: Partial molecular characterization an identity with acidic and basic fibroblast growth factors. Biochemistry 24: 7855–7860; 1985.
Bitensky, M. W.; Demopoulos, H. B.; Russell, V. MSH-responsive adenyl cyclase in the Cloudman S-91 melanoma. Riley, V. ed. Pigmentation, New York: Appleton-Century-Crofts; 1972; 247–255.
Burgess, W. H.; Mehlmann, T.; Friesel, R.; Johnson, W. V.; Maciag, T. Multiple forms of endothelial cell growth factor. J. Biol. Chem. 260: 11389–11392; 1985.
Coussens, L.; Yang-Feng, T. L.; Liao, Y-C.; Chen, E.; Gray, A.; McGrath, J.; Seeburg, P. H.; Libermann, T. A.; Schlessinger, J.; Francke, U.; Levinson, A.; Ullrich, A. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location withnew oncogene. Science 230: 1132–1139; 1985.
Downward, J.; Yarden, Y.; Mayes, E.; Scrace, G.; Totty, N.; Stockwell, P.; Ulrich, A.; Schlessinger, J.; Waterfield, M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature (London) 307: 521–527; 1984.
Eisinger, E.; Marko, O. Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin. Proc. Natl. Acad. Sci. USA 79: 2018–2022; 1982.
Eisinger, E.; Marko, O.; Ogata, S-I.; Old, L. J. Growth regulation of human melanocytes. Science 229: 984–986; 1984.
Esch, F.; Baird, A.; Ling, N.; Ueno, N.; Hill, F.; Denoroy, L.; Klepper, R.; Gospodarowicz, D.; Bohlen, P.; Guillemin, R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the aminoterminal sequence of bovine brain acidic FGF. Proc. Natl. Acad. Sci. USA 82: 6507–6511; 1985.
Gimenez-Gallego, G.; Rodkey, J.; Bennett, C.; Rios-Candelore, M.; DiSalvo, J.; Thomas, K. Brain-derived acidic fibroblast growth factor: Complete amino acid sequence and homologies. Science 230: 1385–1388; 1985.
Gospodarowicz, D.; Cheng, J.; Lui, G.-M.; Baird, A.; Bohlen, P. Isolation of brain fibroblast growth factor by heparin-Sepharose affinity chromatography: Identity with pituitary fibroblast growth factor. Proc. Natl. Acad. Sci. USA 81: 6963–6967; 1984.
Gospodarowicz, D.; Cheng, J.; Lui, G-M.; Fuji, D. K.; Baird, A.; Bohlen, P. Fibroblast growth factor in the human placenta. Biochem. Biophys. Res. Commun. 128: 554–562; 1985.
Green, S.; Walter, P.; Kumar, V.; Krust, A.; Bornert, J.-M.; Argos, P.; Chambon, P., Human oestrogen receptor cDNA: Sequence, expression and homology to v-erb-A. Nature (London) 320:134–139; 1986.
Halaban, R.; Alfano, F. D. Selective elimination of fibroblasts from cultures of normal human melanocytes. In Vitro 20: 447–450; 1984.
Halaban, R.; Ghosh, S.; Duray, P.; Kirkwood, J. M.; Lerner, A. B. Human melanocytes cultured from nevi and melanomas. J. Invest. Dermatol. 87: 95–101; 1986.
Jaye, M.; Howk, R.; Burgess, W.; Ricca, G. A.; Chiu, L-M.; Ravera, M. W.; O’Brien, S. J.; Modi, W. S.; Maciag, T.; Drohan, W. N. Human endothelial cell growth factor: Cloning nucleotide sequence, and chromosome localization. Science 233: 541–545; 1986.
Klagsburn, M.; Sasse, J.; Smith, J. A. Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. Proc. Natl. Acad. Sci. USA 83: 2448–2452; 1986.
Maciag, T.; Mehlman, T.; Frisel, R.; Schreiber, A. B. Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain. Science 225: 932–935; 1984.
Moenner, M.; Chevallier, B.; Badet, J.; Barritault, D. Evidence and characterization of the receptor to eye-derived growth factor I, the retinal form of basic fibroblast growth factor, on bovine epithelial lens cells. Proc. Natl. Acad. Sci. USA 83: 5024–5028; 1986.
Neufeld, G.; Gospodarowicz, D. Basic and acidic fibroblast growth factors interact with the same cell surface receptors. J. Biol. Chem. 261: 5631–5637; 1986.
Olwin, B. B.; Hauschka, S. D. Identification of the fibroblast growth factor receptor of Swiss 3T3 cells and mouse skeletal muscle myoblasts. Biochemistry 25: 3487–3492; 1986.
Pawelek, J.; Wong, G.; Sansone, M.; Morowitz, J. Molecular controls in mammalian pigmentation. Yale J. Biol. Med. 46: 438–443; 1973.
Robins, K. C.; Antoniades, N. H.; Deare, S. G.; Hunkapillar, M. W.; Aaronson, S. A. Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor. Nature (London) 305: 605–608; 1983.
Schreiber, A.; Kenney, J.; Kowalski, J.; Thomas, K. A. Gimenez-Gallego, G.; Rios-Candelore, M.; Di Salvo, J.; Barritault, D.; Courty, J.; Courtois, Y.; Moenner, M.; Loret, C.; Burgess, W. H.; Mehlman, T.; Friesel, R.; Johnson, W.; Maciag, T. A unique family of endothelial cell polypeptide mitogens: The antigenic and receptor cross-reactivity of bovine endothelial cell growth factor, brain-derived acidic fibroblast growth factor, and eye-derived growth factor-II. J. Cell Biol. 101: 1623–1626; 1985.
Shing, Y.; Folkman, J.; Sullivan, R.; Butterfield, C.; Murray, J.; Klagsburn, M. Heparin affinity: Purification of a tumorderived capillary endothelial cell growth factor. Science 223: 1296–1299; 1984.
Thomas, K. A.; Rios-Candelore, M.; Fitzpatrick, S. Purification and characterization of acidic fibroblast growth factor from bovine brain. Proc. Natl. Acad. Sci. USA 81: 357–361; 1984.
Thomas, K. A.; Rios-Candelore, M.; Gimenez-Gallego, G.; DiSalvo, J.; Bennett, C.; Rodkey, J.; Fitzpatrick, S. Pure brain-derived acidic fibroblast growth factor in a potent angiogenic vascular endothelial cell mitogen with sequence homology to interleukin 1. Proc. Natl. Acad. Sci. USA 82: 6409–6413; 1985.
Wilkins, L.; Gilchrest, B. A.; Szabo, G.; Weinstein, R.; Maciag, T. The stimulation of normal human melanocyte proliferation in vitro by melanocyte growth factor from bovine brain. J. Cell Physiol. 122: 350–361; 1985.
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This work was supported by the Ruth Estrin Memorial for Cancer Research and NIH Grant 5R10 CA04679-26.
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Halaban, R., Ghosh, S. & Baird, A. bFGF is the putative natural growth factor for human melanocytes. In Vitro Cell Dev Biol 23, 47–52 (1987). https://doi.org/10.1007/BF02623492
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DOI: https://doi.org/10.1007/BF02623492