Abstract
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Albino P, Davis BM, Nanus DM (1991) Induction of growth factor RNA expression in human malignant melanoma: markers of transformation. Cancer Res 51:4815–4820
Arita Y, O’Driscoll KR, Weinstein BI (1992) Growth of human melanocyte cultures supported by 12–0-tetradecanoylphorbol-13-acetate is mediated through protein kinase C activation. Cancer Res 52:4514–4521
Becker D, Meier CB, Herlyn M (1989) Proliferation of human malignant melanomas is inhibited by antisense oligonucleotides targeted against basic fibroblast growth factor. EMBO J 8:3685–3691
Becker D, Lee PL, Rodeck U, Herlyn M (1992) Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation. Oncogene 7:2303–2313
Bordoni R, Fine R, Murray D, Richmond A (1990) Characterization of the role of melanoma growth stimulatory activity (MGSA) in the growth of normal melanocytes, nevocytes, and malignant melanocytes. J Cell Biochem 44:207–219
Carpenter G, Cohen S (1979) Epidermal growth factor. Annu Rev Biochem 48: 193–216
Cheifetz S, Weatherbee JA, Tsang ML, Anderson JK, Mole JE, Lucas R, Massague J (1987) The transforming growth factor-beta system, a complex pattern of cross-reactive ligands and receptors. Cell 48:409–415
Chenevix-Trench G, Martin NG, Ellem KAO (1990) Gene expression in melanoma cell lines and cultured melanocytes: correlation between levels of c-src-1, c-myc and p53. Oncogene 5:1187–1193
Dotto GP, Moelmann G, Ghosh S, Edwards M, Halaban R (1989) Transformation of murine melanocytes by basic fibroblast growth factor cDNA and oncogenes and selective suppression of the transformed phenotype in a reconstituted cutaneous enviroment. J Cell Biol 109:3115–3128
Eisinger M, Marco O (1982) 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
Fabricant RN, DeLarco JE, Todaro GJ (1977) Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci USA 74:565–569
Fisher PB, Miranda AF, Babiss LE (1986) Measurement of the effect of interferons on cellular differentiation in murine and human melanoma cells. Methods Enzymol 119:611–618
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 3:197–209
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–237S
Garbe C, Kreuser ED, Zouboulis CC, Stadler R, Orfanos CE (1992) Combined treatment of metastatic melanoma with interferons and cytotoxic drugs. Semin Oncol 19 [Suppl 4]:63–69
Halaban R, Kwon BS, Ghosh S, Delli Bovi P, Baird A (1988a) bFGF as an autocrine growth factor for human melanomas. Oncogene Res 3:177–186
Halaban R, Langdon R, Birchall N, Cuono C, Baird A, Scott G, Moellmann G, McGuire J (1988b) Basic fibroblast growth factor from human keratinocytes is a natural mitogen for melanocytes. J Cell Biol 107:1611–1619
Halaban R, Rubin JS, Funasaka Y, Cobb M, Boulton T, Faletto D, Rosen E, Chan A, Yoko K, White W et al (1992a) Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells. Oncogene 7:2195–2206
Halaban R, Fan B, Ahn J, Funasaka Y, Gitay Goren H, Neufeld G (1992b) Growth factors, receptor kinases, and protein tyrosine phosphatases in normal and malignant melanocytes. J Immunother 12:154–161
Herlyn M, Thurin J, Balaban G, Benicelli JL, Herlyn D, Elder DE, Bondi E, Guerry D, Nowell P, Clark WH, Koprowski H (1985) Characteristics of cultured human melanocytes isolated from different stages of tumor progression. Cancer Res 45:5670–5676
Herlyn M, Kath R, Williams N, Valyi-Nagy I, Rodeck U (1990) Growth-regulatory factors for normal, premalignant and malignant human cells in vitro. Adv Cancer Res 54:213–234
Kim MK, Warren TC, Kimball ES (1985) Purification and characterization of a low molecular weight transforming growth factor from the urine of melanoma patients. J Biol Chem 260:9237–9243
Krasagakis K, Garbe C, Krüger S, Orfanos CE (1991) Effects of interferons on cultured human melanocytes in vitro: interferon-beta but not -alpha or –gamma inhibit proliferation and all interferons significantly modulate the cell phenotype. J Invest Dermatol 97:364–372
Krasagakis K, Garbe C, Krüger-Krasagakes S, Orfanos CE (1993) 12–0 tetra-decanoylphorbol-13-acetate not only modulates proliferation rates but also alters antigen expression and LAK-cell susceptibility of normal human melanocytes in vitro. J Invest Dermatol 100:653–659
Lawson DH, Thomas HG, Roy RGB, Gordon DS, Chawla RK, Nixon DW, Richmond A (1987) Preparation of a monoclonal antibody to melanoma growth stimulatory activity released into serum-free culture medium by Hs0294 malignant melanoma cells. J Cell Biochem 34:169–185
Lu C, Kerbel RS (1993) Interleukin 6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression. J Cell Biol 120:1281–1288
Lu C, Vickers MF, Kerbel RS (1992) Interleukin 6: a fibroblast derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression. Proc Natl Acad Sci USA 89:9215–9219
Mather JP, Sato GH (1979) The growth of mouse melanoma cells in hormone-supplemented, serum-free medium. Exp Cell Res 120:191–200
Mooradian DL, Purchio AF, Furcht LT (1990) Differential effects of transforming growth factor β 1 on the growth of poorly and highly metastatic murine melanoma cells. Cancer Res 50:273–277
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 45:334–341
Nakai S, Mizuno K, Kaneta M, Hirai Y (1988) A simple, sensitive bioassay for the detection of interleukin-1 using human melanoma A375 cell line. Biochem Biophys Res Commun 154:1189–1196
Peacocke M, Yaar M, Mansur CP, Chao MV, Gilchrest BA (1988) Induction of nerve growth factor receptors on cultured human melanocytes. Proc Natl Acad Sci USA 85:5282–5286
Richmond A, Thomas HG (1988) Melanoma growth stimulatory activity: isolation from human melanoma tumors and characterization of tissue distribution. J Cell Biochem 36:185–198
Richmond A, Balentien E, Thomas HG, Flaggs G, Barton DE, Spiess J, Bordoni R, Francke R, Derynck R (1988) Molecular characterisation and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to β-thromboglobulin. EMBO J 7:2025–2033
Rodeck U, Herlyn, M, Menssen HD, Furlanetto RW, Koprowski H (1987) Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors. Int J Cancer 40:687–690
Rodeck U, Melber K, Kath R, Menssen H-D, Varello M, Atkinson B, Herlyn M (1991) Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes. J Invest Dermatol 97:20–26
Sauvaigo S, Fretts RE, Riopelle RJ, Lagard AE (1986) Autonomous proliferation of MeWo human melanoma cell lines in serum-free medium: secretion of growth-stimulating activities. Int J Cancer 37:123–132
Schadendorf D, Möller A, Algermissen B, Worm M, Sticherling M, Czarniecki BM (1993) IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J Immunol 151:2667–2675
Sun WH, Kreisle RA, Phillips AW, Ershler WB (1992) In vivo and in vitro characteristics of interleukin 6-transfected B16 melanoma cells. Cancer Res 52:5412–5415
Swope VB, Abdel-Malek Z, Kassem LM, Nordlund JJ (1991) Interleukins 1 alpha and 6 and tumor necrosis factor-alpha are paracrine inhibitors of human melanocyte proliferation and melanogenesis. J Invest Dermatol 96:180–185
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 11–25
Turner AM, Zsebo KM, Martin F, Jacobsen FW, Bennett LG, Broudy VC (1992) Nonhematopoietic tumor cells express stem cell factor and display c-kit receptors. Blood 80:374–381
Tyring SK, Klimpel G, Brysk M (1984) Eradication of cultured human melanoma cells by immune interferon and leukocytes. J Natl Cancer Inst 73:1067–1073
Wadler S, Schwartz EL (1990) Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental and human malignancies: a review. Cancer Res 50:3473–3486
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 5:137–145
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–230S
Zouboulis CC, Garbe C, Krasagakis K, Krüger S, Orfanos CE (1991) A fluorometric rapid microassay to identify antiproliferative compounds for human melanoma cells in vitro. Melanoma Res 1:91–95
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer-Verlag Berlin · Heidelberg
About this paper
Cite this paper
Krasagakis, K., Garbe, C., Zouboulis, C.C., Orfanos, C.E. (1995). Growth Control of Melanoma Cells and Melanocytes by Cytokines. In: Garbe, C., Schmitz, S., Orfanos, C.E. (eds) Skin Cancer: Basic Science, Clinical Research and Treatment. Recent Results in Cancer Research, vol 139. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78771-3_12
Download citation
DOI: https://doi.org/10.1007/978-3-642-78771-3_12
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-78773-7
Online ISBN: 978-3-642-78771-3
eBook Packages: Springer Book Archive