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Production of Cytokines by Human Melanoma Cells and Melanocytes

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Book cover Skin Cancer: Basic Science, Clinical Research and Treatment

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 139))

Abstract

Experimental animal models have shown that various cytokines, depending on their specific properties, may support growth and metastasis of tumor cells or even lead to tumor rejection. The analysis of expression of cytokine genes by melanoma cell lines indicated that melanoma cells constitutively produce both autostimulatory and inhibitory cytokines. Using reverse transcriptase polymerase chain reaction analysis, simultaneous expression of several cytokines, including interleukin-1 beta (IL-1β), IL-6, IL-8, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor, by melanoma cells was found. The same cytokine transcripts were detected in melanocytes, suggesting that cells of the melanocytic lineage express a specific pattern of cytokines in vitro. All these cytokines are known to be able to stimulate effector cells of the host. Additionally, production of mRNA for IL-10, a cytokine with potential immunosuppressive properties, was detected in melanoma cells and melanocytes. These and other cytokines are likely to be involved in the immune response to cancer and at this time it is unknown what the net effects of multiple cytokines are on the outcome of the host response to tumor.

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References

  • Armstrong CA, Tara DC, Hart CE, Köck A, Luger TA, Ansel JC (1992) Heterogeneity of cytokine production by human malignant melanoma cells. Exp Dermatol 1:37–45

    Article  PubMed  CAS  Google Scholar 

  • Asher AL, Mule JJ, Kasid A, Restifo NP, Salo JC, Reichert CM, Jaffe G, Fendly B, Kriegler M, Rosenberg SA (1991) Murine tumor cells transduced with the gene for tumor necrosis factor alpha. J Immunol 146:3227–3234

    PubMed  CAS  Google Scholar 

  • Bennicelli JL, Elias J, Kern J, Guerry D (1989) Production of interleukin 1 activity by cultured human melanoma cells. Cancer Res 49:930–935

    PubMed  CAS  Google Scholar 

  • Blankenstein T, Qin Z, Überla K, Müller W, Rosen H, Volk H-D, Diamantstein T (1991) Tumor suppression after tumor cell targeted tumor necrosis factor alpha gene transfer. J Exp Med 173:1047–1052

    Article  PubMed  CAS  Google Scholar 

  • Burrows FJ, Haskard DO, Bart IR (1991) Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions. Cancer Res 51:4768–4775

    PubMed  CAS  Google Scholar 

  • Chevenix-Trench G, Martin NG, Ellem KAO (1990) Gene expression in melanoma cell lines and cultured melanocytes: correlation between level of c-src-1, c-myc and p53. Oncogene 5:1187–1193

    Google Scholar 

  • Colombo MP, Ferrari G, Stoppacciaro A, Parenza M, Rodofo M, Mavilio F, Par-miani G (1991) Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med 173:889–897

    Article  PubMed  CAS  Google Scholar 

  • Colombo MP, Maccalli C, Mattei S, Melani C, Radrizzani M, Parmiani G (1992) Expression of cytokine genes, including IL-6, in human malignant melanoma cell lines. Melanoma Res 2:181–189

    Article  PubMed  CAS  Google Scholar 

  • De Waal-Malefyt R, Abrams J, Bennet B, Figdor CG, De Vries J (1991a) Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209–1220

    Article  PubMed  Google Scholar 

  • De Waal-Malefyt R, Haanen J, Spits H, Roncarolo M-G, Te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, De Vries JE (1991b) Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T-cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174:915–924

    Article  PubMed  Google Scholar 

  • De Waal-Malefyt R, Yssel H, Roncarolo M-G, Spits H, De Vries J (1992) Interleukin-10. Curr Opin Immunol 4:314–320

    Article  PubMed  Google Scholar 

  • Dorsch M, Hock H, Kunzendorf U, Diamantstein T, Blankenstein T (1993) Macrophage colony-stimulating factor gene transfer into tumor cells induces macrophage infiltration but not tumor suppression. Eur J Immunol 23:186–190

    Article  PubMed  CAS  Google Scholar 

  • Douvdevani A, Huleihel M, Zoller M, Segal S, Apte RN (1992) Reduced tumorigenicity of fibrosarcomas which constitutively generate IL-1 alpha either spontaneously or following IL-1 alpha gene transfer. Int J Cancer 51:822–830

    Article  PubMed  CAS  Google Scholar 

  • Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 90:3539–3543

    Article  PubMed  CAS  Google Scholar 

  • Eberle J, Krasagakis K, Garbe C, Orfanos CE (1993) Proliferation and morphology of melanoma cells and benign melanocytes under varying culture conditions. Melanoma Res 3:107–112

    Article  PubMed  CAS  Google Scholar 

  • Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P (1990) Interleukin 2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60:397–403

    Article  PubMed  CAS  Google Scholar 

  • Förster E, Kirnbauer R, Urbanski A, Köck A, Luger TA (1991) Human melanoma cells produce interleukin 8 which functions as an autocrine growth factor. J Invest Dermatol 96:608

    Google Scholar 

  • Gansbacher B, Bannerjii R, Daniels B, Zier K, Cronin K, Gilboa E (1990a) Retroviral vector-mediated interferon-gamma gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 50:7820–7825

    PubMed  CAS  Google Scholar 

  • Gansbacher B, Zier K, Daniels B, Cronin K, Bannerjy R, Gilboa E (1990b) Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 172:1217–1224

    Article  PubMed  CAS  Google Scholar 

  • Gastl GA, Abrams JS, Nannes DM, Oosterkamp R, Silver J, Liu F, Chen M, Albino AP, Bander NH (1993) Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin 6 expression. Int J Cancer 55:96–101

    Article  PubMed  CAS  Google Scholar 

  • Giavazzi R, Garofalo A, Bani MR (1990) Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice. Cancer Res 50:4771–4775

    PubMed  CAS  Google Scholar 

  • Golumbek PT, Lazenby AJ, Levitsky HI, Jaffee LM, Karasuyama H, Baker M, Pardoll DM (1991) Treatment of established renal cancer by tumor cells engineered to secrete interleukin 4. Science 254:713–716

    Article  PubMed  CAS  Google Scholar 

  • Hock H, Dorsch M, Diamantstein T, Blankenstein T (1991) Interleukin 7 induces CD4+ T-cell dependent tumor rejection. J Exp Med 174:1291–1298

    Article  PubMed  CAS  Google Scholar 

  • Kishimoto T (1985) Factors affecting B cell growth and differentiation. Annu Rev Immunol 3:133–157

    Article  PubMed  CAS  Google Scholar 

  • Köck A, Schwarz T, Urbanski A, Peng Z, Vetterlein M, Micksche M, Ansel JC, Kung HF, Luger TA (1989) Expression and release of interleukin-1 by different human melanoma cell lines. J Natl Cancer Inst 81:36–42

    Article  PubMed  Google Scholar 

  • Kolde G, Schulze-Osthoff K, Meyer H, Knop J (1992) Immunohistological and immunoelectron microscopic identification of TNF alpha in normal human and murine epidermis. Arch Dermatol Res 284:154–158

    Article  PubMed  CAS  Google Scholar 

  • Krüger-Krasagakes S, Li W, Richter G, Diamantstein T, Blankenstein T (1993) Eosinophils infiltrating interleukin 5 gene transfected tumors do not suppress tumor growth. Eur J Immunol 23:992–995

    Article  PubMed  Google Scholar 

  • Krüger-Krasagakes S, Krasagakis K, Garbe C, Schitt E, Hüls C, Blankenstein T, Diamanstein T (1994) Expression of interleukin 10 in human melanoma (submitted for publication)

    Google Scholar 

  • Lachman LB, Dinarello CA, Llansa ND, Fidler IJ (1986) Natural and recombinant human interleukin 1 is cytotxic for human melanoma cells. J Immunol 136: 3098–3102

    PubMed  CAS  Google Scholar 

  • Larsen CG, Anderson AO, Appella E, Oppenheim JJ, Matsushima K (1989) The neutrophil-activating protein (NAP-1) is also chemotactic for T-lymphocytes. Science 243:1464–1466

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Lee C, Biondi A, Wang XH, Iscove NN, de Sousa J, Aarden LA, Wong GG, Clark SC, Messner HA, Minden MD (1989) A possible autocrine role for interleukin-6 in two lymphoma cell lines. Blood 74:798–804

    Google Scholar 

  • Lotz M, Jirik F, Kabouridis R, Tsoukas C, Hirano T, Kishimoto T, Carson DA (1988) BSF-2/IL-6 is a costimulant for human thymocytes and T lymphocytes.

    Google Scholar 

  • J Exp Med 167:1253–1258

    Google Scholar 

  • Lu C, Kerbel RS (1993) Interleukin 6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during melanoma progression. J Cell Biol 120:1281–1288

    Article  PubMed  CAS  Google Scholar 

  • Lugassy C, Escade JP (1991) Immunolocation of TNF-a/Cachectin in human melanoma cells: studies on co-cultivated malignant melanoma. J Invest Dermatol 96:238–242

    Article  PubMed  CAS  Google Scholar 

  • Luster AD, Leder P (1993) IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo. J Exp Med 178:1057–1065

    Article  PubMed  CAS  Google Scholar 

  • Mizutani H, Miwa N, Mizutani T, Kupper TS (1990) Melanocytes produce IL-1 beta and contain IL-1 beta convertase activity: a potential in vivo mechanism for paracrine conversion of keratinocyte pro-IL-1-beta. J Invest Dermatol 94: 556A

    Google Scholar 

  • Morinaga Y, Suzuki H, Takatsuki F (1989) Contribution of IL-6 to the antiproliferative effect of IL-1 and tumor necrosis factor on tumor cell lines. J Immunol 143:3538–3542

    PubMed  CAS  Google 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 rIL-1 beta, rTNF-alpha, rIFN-gamma, rIL-4 and their combinations. Int J Cancer 45:334–341

    Article  PubMed  CAS  Google Scholar 

  • Mule JJ, Mcintosh JK, Jablons DM, Rosenberg SA (1990) Antitumor activity of recombinant interleukin 6 in mice. J Exp Med 17:629–636

    Article  Google Scholar 

  • Pisa P, Halapi E, Pisa EK, Gerdin E, Hising C, Bucht A, Gerdin B, Kiessling R (1992) Selective expression of interleukin 10, interferon-gamma, and granulocyte-macrophage colony-stimulating factor in ovarian cancer biopsies. Proc Natl Acad Sci USA 89:7708–7712

    Article  PubMed  CAS  Google Scholar 

  • Qin Z, Krüger-Krasagakes S, Kunzendorf U, Hock H, Diamantstein T, Blankenstein T (1993) Expression of tumor necrosis factor by different tumor cell lines results either in tumor suppression or augmented metastasis. J Exp Med 178:355–360

    Article  PubMed  CAS  Google Scholar 

  • Richmond A, Thomas HG (1988) Melanoma growth stimulatory activity: isolation from human melanoma tumors and characterization of tissue distribution. J Cell Biol 36:185–198

    CAS  Google Scholar 

  • Richmond A, Lawson DH, Nixon DW, Stewens JS, Chawia RK (1983) Extraction of a melanoma growth-stimulatory activity from culture medium conditioned by the Hs0294 human melanoma cell line. Cancer Res 43:2106–2112

    PubMed  CAS  Google Scholar 

  • Richmond A, Balentien E, Thomas HG, Flaggs G, Barton DE, Spiess J, Bordoni R, Francke U, Derynck R (1988) Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to β-thromboglobulin. EMBO J 7:2025–2033

    PubMed  CAS  Google Scholar 

  • Richter G, Krüger-Krasagakes S, Hein G, Hüls C, Schmitt E, Diamantstein T, Blankenstein T (1993) Interleukin 10 transfected into Chinese hamster ovary cells prevents tumor growth and macrophage infiltration. Cancer Res 53:4134–4137

    PubMed  CAS  Google Scholar 

  • Robertson B, Gahring L, Newton R, Daynes R (1987) In vivo administration of interleukin 1 to normal mice depresses their capacity to elicit contact hypersensitivity responses: prostaglandins are involved in this modification of immune function. J Invest Dermatol 88:380–387

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Rollins BJ, Sunday ME (1991) Suppression of tumor formation in vivo by expression of the JE gene in malignant cells. Mol Cell Biol 11:3125–3131

    PubMed  CAS  Google Scholar 

  • Sabatini M, Chavez J, Mundy GR, Bonewald LF (1990) Stimulation of tumor necrosis factor release from monocytic cells by the A375 human melanoma via granulocyte-macrophage colony-stimulating factor. Cancer Res 50:2673–2678

    PubMed  CAS  Google Scholar 

  • Schadendorf D, Möller A, Algermissen B, Worm M, Sticherling M, Czarnetzki BM (1993) IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J Immunol 151:2667–2675

    PubMed  CAS  Google Scholar 

  • Sieff CA, Emerson SG, Donahue RE (1985) Human recombinant granulocyte-acrophage colony-stimulating factor: a multilineage hematopoietin. Science 230:1171–1173

    Article  PubMed  CAS  Google Scholar 

  • Sun WH, Kreisle RA, Phillips AW, Ershler WB (1992) In vivo and in vitro characteristics of interleukin 6-tranfected B16 melanoma cells. Cancer Res 52:5412–5415

    PubMed  CAS  Google Scholar 

  • Tepper RI, Pattengale PK, Leder P (1989) Murine interleukin 4 displays potent antitumor activity in vivo. Cell 57:503–512

    Article  PubMed  CAS  Google Scholar 

  • Topalian SL, Solomon D, Rosenberg SA (1989) Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol 142:3714–3719

    PubMed  CAS  Google Scholar 

  • Torre-Amione G, Beauchamp RD, Koeppen H, Park BH, Schreiber H, Moses HL, Rowley DA (1990) A highly immunogenic tumor transfected with a murine transforming growth factor type β1 cDNA escapes immune surveillance. Proc Natl Acad Sci USA 87:1486–1490

    Article  PubMed  CAS  Google Scholar 

  • Van den Ende B, Knuth A, Boon T (1992) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254:1643–1647

    Google Scholar 

  • Vieira P, De Waal-Malefyt R, Dang M-N, Johnson KE, Kastelein R, Fiorentino DF, De Vries JE, Roncarolo M-G, Mosman TR, Moore KW (1991) Isolation and expression of human cytokine-synthesis-inhibitory-factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRF1. Proc Natl Acad Sci USA 88:1172–1176

    Article  PubMed  CAS  Google Scholar 

  • Wang JM, Tarabolett G, Matsushima K, Van Damme J, Mantovani A (1990) Induction of haptotactic migration of melanoma cells by neutrophil activating protein/interleukin-8. Biochem Biophys Res Commun 169:165–170

    Article  PubMed  CAS  Google Scholar 

  • Watanabe Y, Kuribayashi K, Miyatake S, Nishihara K, Nakayama E-I, Taniyama T, Sakata T-A (1989) Exogenous expression of mouse interferon-gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. Proc Natl Acad Sci USA 86:9456–9460

    Article  PubMed  CAS  Google Scholar 

  • Yamamura M, Uvemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL (1991) Defining protective responses to pathogens: cytokine profiles in leprosy skin. Science 254:277–279

    Article  PubMed  CAS  Google Scholar 

  • Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, Leonard EJ (1987) Purification of a human monocyte-derived neutrophil chemo-tactic factor that shares sequence homology with other host defence cytokines. Proc Natl Acad Sci USA 84:9233–9237

    Article  PubMed  CAS  Google Scholar 

  • Zachariae COC, Thestrup-Pedersen K, Matsushima K (1991) Expression and secretion of leukocyte chemotactic cytokines by normal human melanocytes and melanoma cells. J Invest Dermatol 97:593–599

    Article  PubMed  CAS  Google Scholar 

  • Zouboulis CC, Schröder K, Garbe C, Krasagakis K, Krüger S, Orfanos CE (1990) 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

    Article  PubMed  CAS  Google Scholar 

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© 1995 Springer-Verlag Berlin · Heidelberg

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Krüger-Krasagakes, S., Krasagakis, K., Garbe, C., Diamantstein, T. (1995). Production of Cytokines by Human Melanoma Cells and Melanocytes. 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_11

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  • DOI: https://doi.org/10.1007/978-3-642-78771-3_11

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