Growth Control of Melanoma Cells and Melanocytes by Cytokines
Aberrant proliferation of tumor cells characterizes cancer growth. Investigations of cellular growth control mechanisms have contributed to our understanding of carcinogenesis and to the identification of compounds with specific antitumor activity. Many cytokines have been found to act on melanoma tumors, either produced by the tumor cells themselves or by infiltrating host cells. Purified cytokines allowed direct comparison of the growth response between normal human melanocytes and malignant melanoma cells. The present paper summarizes results of a series of our own experiments not yet published and data from a review of the recent literature. Proliferation of normal human melanocytes is enhanced by several cytokines, including basic fibroblast growth factor (bFGF), melanoma growth stimulatory activity (MGSA), hepatocyte growth factor (HGF), and mast cell growth factor (MGF). Melanoma cells are additionally stimulated by epidermal growth factor (EGF)/transforming growth factor alpha (TGF-α) and nerve growth factor (NGF). Tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β 1), and interleukin (IL)-6 are all potent inhibitors of melanocyte growth, but they are less effective on melanoma cells or even stimulate their growth. Interferon (IFN)-α and IFN-γ inhibited proliferation of melanoma cells but not of melanocytes, whereas IFN-β showed antiproliferative effects in both cell types. These findings suggest an alteration in growth control mechanisms during melanocyte transformation and possibly play a role in melanoma pathogenesis.
KeywordsAlbumin Tyrosine Hydrocortisone Oncol Polypeptide
Unable to display preview. Download preview PDF.
- Funasaka Y, Boulton T, Cobb M, Yarden Y, Fan B, Lyman SD, Williams DE, Anderson DM, Zakut R, Mishima Y, Halaban R (1992) c-Kit-kinase induces a cascade of protein tyrosine phosphorylation in normal human melanocytes in response to mast cell growth factor and stimulates mitogen-activated protein kinase but is down-regulated in melanomas. Mol Biol Cell 3:197–209PubMedGoogle Scholar
- Garbe C, Krasagakis K, Zouboulis CC, Schröder K, Krüger S, Stadler R, Orfanos CE (1990) Antitumor activities of interferon alpha, beta and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis and immunophenotype. J Invest Dermatol 95:23IS–237SCrossRefGoogle Scholar
- Mortarini R, Belli F, Parmiani G, Anichini A (1990) Cytokine-mediated modulation of HLA-class II, ICAM-1, LFA-3 and tumor-associated antigen profile of melanoma cells. Comparison with anti-proliferative activity by rIL1-beta, rTNF-alpha, rIFN-gamma, rIL4 and their combinations. Int J Cancer 45:334–341PubMedCrossRefGoogle Scholar
- Todaro GJ (1988) Oncogenes and growth factors. In: Orfanos CE, Stadler R, Gollnick H (eds) Dermatology in five continents. Springer, Berlin Heidelberg New York, pp 11–25Google Scholar
- Zouboulis CC, Garbe C, Krüger S, Orfanos CE (1990a) Interferons and melanoma: comparison of the cytostatic and cytotoxic effects of natural and recombinant interferons, tumor necrosis factor-alpha and their combinations on human melanoma cells in vitro. Skin Cancer 5:137–145Google Scholar
- Zouboulis CC, Schröder K, Garbe C, Krasagakis K, Krüger S, Orfanos CE (1990b) Cytostatic and cytotoxic effects of recombinant tumor necrosis factor-alpha on sensitive human melanoma cells in vitro may result in selection of cells with enhanced markers of malignancy. J Invest Dermatol 95:223S–230SPubMedCrossRefGoogle Scholar