Skip to main content

Role of Cytokines in Pathology of Melanoma and Use of Biologic Response Modifiers in Melanoma

  • Protocol
Melanoma Techniques and Protocols

Part of the book series: Methods in Molecular Medicine ((MIMM,volume 61))

  • 463 Accesses

Abstract

Growth of normal cells is regulated by polypeptides that act via specific cellular receptors. Otherwise known as cytokines, these substances include the growth factors that modulate the proliferation of nonimmune cells. Lymphokines or cytokines, on the other hand, are involved in the regulation of immune cells. Advances in the last 15 yr have shown that alterations in cytokines and their receptors may play a central role in the uncontrolled proliferation of tumor cells in vitro, and such cytokine aberrations are possibly responsible for regulation of tumor growth in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sauvaigo, S., Fretts, R. E., Riopelle, R. J., and Lagard, A. E. (1986) Autonomous proliferation of MeWo human melanoma cell lines in serum-free medium: secretion of growth-stimulating activities. Int. J. Cancer 37, 123–132.

    Article  PubMed  CAS  Google Scholar 

  2. Rodeck, U., Melber, K., Kath, R., Menssen, H.-D., Varello, M., Atkinson, B., and 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 

  3. Richmond, A., Balentien, E., Thomas, H. G., Flaggs, G., Barton, D. E., Spiess, J., Bordoni, R., Franke, R., and 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 

  4. Richmond, A., Lawson, D. H., Nixon, D. W., Stewens, J. S., and Chawia, R. K. (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 

  5. Chenevix-Trench, G., Martin, N. G., and Ellem, K. A. O. (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.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Bordoni, R., Fine, R., Murray, D., and 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.

    Article  PubMed  CAS  Google Scholar 

  8. Lawson, D. H., Thomas, H. G., Roy, R. G. B., Gordon, D. S., Chawla, R. K., Nixon, D. W., and 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 

  9. Kruger-Krasagakes, S., Krasagakis, K., Garbe, C., and Diamantstein, T. (1995) Production of cytokines by human melanoma cells and melanocytes. Recent Results Cancer Res. 139, 155–168.

    Article  PubMed  CAS  Google Scholar 

  10. Colombo, M. P., Maccalli, C., Mattei, S., Melani, C., Radrizzani, M., and 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 

  11. Schadendorf, D., Moller, A., Algermissen, B., Worm, M., Sticherling, M., and Czarniecki, B. M. (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 

  12. Zachariae, C. O. C., Thestrup-Pedersen, K., and 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 

  13. Forster, E., Kirnbauer, R., Urbanski, A., Kock, A., and Luger, T. A. (1991) Human melanoma cells produce interleukin 8 which functions as an autocrine growth factor. J. Invest. Dermatol. 96, 608.

    Google Scholar 

  14. Yoshimura, T., Matsushima, K., Tanaka, S., Robinson, E. A., Appella, E., Oppenheim, J. J., and Leonard, E. J. (1987) Purification of a human monocyte-derived neutrophil chemotactic factor that shares sequence homology with other host defensed cytokines. Proc. Natl. Acad. Sci. USA 84, 9233–9237.

    Article  PubMed  CAS  Google Scholar 

  15. Larsen, C. G., Anderson, A. O., Appella, E., Oppenheim, J. J., and Matsushima, K. (1989) The neutrophil-activating protein (NAP-1) is also chemotactic for T-lymphocytes. Science 243, 1464–1466.

    Article  PubMed  CAS  Google Scholar 

  16. Wang, J. M., Tarabolett, G., Matsushima, K., Van Damme, J., and 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 

  17. Halaban, R., Langdon, R., Birchall, N., Cuono, C., Baird, A., Scott, G., Moellmann, G., and McGuire, J. (1988) Basic fibroblast growth factor from human keratinocytes is a natural mitogen for melanocytes. J. Cell Biol. 107, 1611–1619.

    Article  PubMed  CAS  Google Scholar 

  18. Stocker, K. M., Sherman, L., Rees, S., and Ciment, G. (1991) Basic FGF and TGF-β1 influence commitment to melanogenesis in neural crest-derived cells of avian embryos. Development 111, 635–645.

    PubMed  CAS  Google Scholar 

  19. Halaban, R., Kwon, B. S., Ghosh, S., Delli Bovi, P., and Baird, A. (1988) bFGF as an autocrine growth factor for human melanomas. Oncogene Res. 3, 177–186.

    PubMed  CAS  Google Scholar 

  20. Becker, D., Meier, C. B., and Herlyn, M. (1989) Proliferation of human malignant melanomas is inhibited by antisense oligonucleotides targeted against basic fibroblast growth factor. EMBO J. 8, 3685–3691.

    PubMed  CAS  Google Scholar 

  21. Becker, D., Lee, P. L., Rodeck, U., and 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.

    PubMed  CAS  Google Scholar 

  22. Halaban, R., Fan, B., Ahn, J., Funasaka, Y., Gitay Goren, H., and Neufeld, G. (1992) Growth factors, receptor kinases, and protein tyrosine phosphatases in normal and malignant melanocytes. J. Immunother. 12, 154–161.

    Article  PubMed  CAS  Google Scholar 

  23. Dotto, G. P., Moelmann, G., Ghosh, S., Edwards, M., and 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 environment. J. Cell Biol. 109, 3115–3128.

    Article  PubMed  CAS  Google Scholar 

  24. Krasagakis, K., Garbe, C., Zouboulis, C. C., and Ofanos, C. E. (1995) Growth control of melanoma cells and melanocytes by cytokines. Recent Results Cancer Res. 139, 169–182.

    Article  PubMed  CAS  Google Scholar 

  25. Carpenter, G. and Cohen, S. (1979) Epidermal growth factor. Annu. Rev. Biochem. 48, 193–216.

    Article  PubMed  CAS  Google Scholar 

  26. Herlyn, M., Kath, R., Williams, N., Valyi-Nagy, I., and Rodeck, U. (1990) Groth-regulatory factors for normal, premalignant and malignant human cells in vitro. Adv. Cancer Res. 54, 213–234.

    Article  PubMed  CAS  Google Scholar 

  27. Albino, P., Davis, B. M. and Nanus, D. M. (1991) Induction of growth factor RNA expression in human malignant melanoma: markers of transformation. Cancer Res. 51, 4815–4820.

    PubMed  CAS  Google Scholar 

  28. Rodeck, U., Herlyn, M., Menssen, H. D., Furlanetto, R. W., and Koprowski, H. (1987) Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors. Int. J. Cancer 40, 687–690.

    Article  PubMed  CAS  Google Scholar 

  29. Cheifetz, S., Weatherbee, J. A., Tsang, M. L., Anderson, J. K., Mole, J. E., Lucas, R., and Massague, J. (1987) The transforming growth factor-beta system, a complex pattern of cross-reactive ligands and receptors. Cell 48, 409–415.

    Article  PubMed  CAS  Google Scholar 

  30. Mooradian, D. L., Purchio, A. F., and Furcht, L. T. (1990) Differential effects of transforming growth factor α1 on the growth of poorly and highly metastatic murine melanoma cells. Cancer Res. 50, 273–277.

    PubMed  CAS  Google Scholar 

  31. Fabricant, R. N., DeLarco, J. E., and Todaro, G. J. (1977) Nerve growth factor receptors on human melanoma cells in culture. Proc. Natl. Acad. Sci. USA 74, 565–569.

    Article  PubMed  CAS  Google Scholar 

  32. Herlyn, M., Thurin, J., Balaban, G., Genicelli, J. L., Herlyn, D., Elder, D. E., Bondi, E., Guerry, D., Nowell, P., Clark, W. H., and Koprowski, H. (1985) Characteristics of cultured human melanocytes isolated from different stages of tumor progression. Cancer Res. 45, 5670–5676.

    PubMed  CAS  Google Scholar 

  33. Peacocke, M., Yaar, M., Mansur, C. P., Chao, M. V., and Gilchrest, B. A. (1988) Induction of nerve growth factor receptors on cultured human melanocytes. Proc. Natl. Acad. Sci. USA 85, 5282–5286.

    Article  PubMed  CAS  Google Scholar 

  34. Krasagakis, K., Garbe, C., Kruger-Krasagakes, S., and Orfanos, C. E. (1993) 12-O tetradecanoylphorbol-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.

    Article  PubMed  CAS  Google Scholar 

  35. Mather, J. P. and Sato, G. H. (1979) The growth of mouse melanoma cells in hormone-supplemented, serum-free medium. Exp. Cell Res. 120, 191–200.

    Article  PubMed  CAS  Google Scholar 

  36. Halaban, R., Rubin, J. S., Funasaka, Y., et al. (1992) Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells. Oncogene 7, 2195–2206.

    PubMed  CAS  Google Scholar 

  37. Sargent, N. S., Oestreicher, M., Haidvogl, H., Madnick, H. M., and Burger, M. M. (1988) Growth regulation of cancer metastases by their host organ. Proc. Natl. Acad. Sci. USA 85, 7251–7255.

    Article  PubMed  CAS  Google Scholar 

  38. Vieira, P., De Waal-Malefyt, R., Dang, M.-N., Johnson, K. E., Kastelein, R., Fiorentino, D. F., De Vries, J. E., Roncarolo, M.-G., Mosman, T. R., and Moore, K. W. (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 

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

    Article  PubMed  Google Scholar 

  40. Ralph, P., Nakoinz, I., Sampson-Johannes, A., Fong, S., Lowe, D., Min, H.-Y., and Lin, L. (1992) IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J. Immunol. 148, 808–814.

    PubMed  CAS  Google Scholar 

  41. De Waal-Malefyt, R., Haanen, J., Spits, H., Roncardo, M.-G., Te Velde, A., Figdor, C., Johnson, K., Kastelein, R., Yssel, H., and De Vries, J. E. (1991) 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.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  43. Pisa, P., Halapi, E., Pisa, E. K., Gerdin, E., Hising, C., Bucht, A., Gerdin, B., and 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 

  44. Gastl, G. A., Abrams, J. S., Nannes, D. M., Oosterkamp, R., Silver, J., Liu, F., Chen, M., Albino, A. P., and Bander, N. H. (1993) Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin 6 expression. Int. J. Cancer 5, 96–101.

    Article  Google Scholar 

  45. Kruger-Krasagakes, S., Krasagakis, K., Garbe, C., Schmitt, E., Huls, C., Blankenstein, T., and Diamantstein, T. (1994) Expression of interleukin 10 in human melanoma. Br. J. Cancer 70, 1182–1185.

    Article  PubMed  CAS  Google Scholar 

  46. Richter, G., Kruger-Krasagakes, S., Hein, G., Huls, C., Schmitt, E., Diamanststein, T., and 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 

  47. Ladanyi, A., Nagy, N. O., Jeney, A., and Timar, J. (1998) Cytokine sensitivity of metastatic human melanoma cell lines—simultaneous inhibition of proliferation and enhancement of gelatinase activity. Pathol. Oncol. Res. 4, 108–114.

    Article  PubMed  CAS  Google Scholar 

  48. Rosenberg, S. A., Mule, J. J., Speiss, P. J., Reichert, C. M., and Schwarz, S. L. (1985) Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin-2. J. Exp. Med. 161, 1169–1188.

    Article  PubMed  CAS  Google Scholar 

  49. Brunda, J. M., Luistro, L., Warrier, R. R., Wright, R. B., Hubbard, B. R., Murphy, M., Wolf, S. F., and Gately, M. K. (1993) Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J. Exp. Med. 178, 1223–1230.

    Article  PubMed  CAS  Google Scholar 

  50. Armstrong, C. A., Tara, D. C., Hart, C. E., Kock, A., Luger, T. A., and Ansel, J. C. (1992) Heterogeneity of cytokine production by human malignant melanoma cells. Exp. Dermatol. 1, 37–45.

    Article  PubMed  CAS  Google Scholar 

  51. Sabatini, M., Chavez, J., Mundy, G. R., and Bonewald, L. F. (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 

  52. Sieff, C. A., Emerson, S. G., and Donahue, R. E. (1985) Human recombinant granulocyte-macrophage colony-stimulating factor: a multilineage hematopoietin. Science 230, 1171–1173.

    Article  PubMed  CAS  Google Scholar 

  53. Colombo, M. P., Maccalli, C., Mattei, S., Melani, S., Radrizzani, M., and Parmiani, G. (1992) Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T lymphocyte cross-talk. Cancer Res. 52, 4853–4857.

    PubMed  CAS  Google Scholar 

  54. Wagner, S. N., Schultewolter, T., Wagner, C., Briedigkeit, L., Becker, J. C., Kwasnicka, H. M., and Goos, M. (1998) Immune response against human primary malignant melanoma: a distinct cytokine mRNA profile associated with spontaneous regression. Lab. Invest. 78, 541–550.

    PubMed  CAS  Google Scholar 

  55. Dranoff, G., Jaffee, E., Lazenby, A., Golumbek, P., Levitsky, H., Brose, K., Jackson, V., Hamada, H., Pardoll, D., and Mulligan, R. C. (1993) Vaccination with irradiated tumor cells engineered to secrete murine granuloctye-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 

  56. Armstrong, C. A., Botella, R., Galloway, T. H., Murray, N., Kramp, J. M., Song, I. S., and Ansel, J. C. (1996) Antitumor effects of granulocyte-macrophage colony-stimulating factor production by melanoma cells. Cancer Res. 56, 2191–2198.

    PubMed  CAS  Google Scholar 

  57. Frank, S. J. and Meyers, M. (1995) Interferons as adjuvant therapy for high risk melanoma. Melanoma Lett. 13, 1–4.

    Google Scholar 

  58. Parkinson, D. R., Houghton, A. N., Hersey, P., et al. (1992) Biologic Therapy for Melanoma, in Cutaneous Melanoma, 2nd ed. (Balch, C. W., Houghton, A. N., Milton, G. W., et al., eds.), Lippincott, Philadelphia, pp. 523,524.

    Google Scholar 

  59. Kirkwood, J. and Ernstoff, M. (1990) Role of interferons in the therapy of melanoma. J. Invest. Dermatol. 95, 180s–184s.

    Article  PubMed  CAS  Google Scholar 

  60. Sidky, Y. A. and Borden, E. C. (1987) Inhibition of angiogenesis by interferons: effects on tumor-and lymphocyte-induced vascular responses. Cancer Res. 47, 5255–5261.

    Google Scholar 

  61. Tyring, S. K., Klimpel, G., and Grysk, M. (1984) Eradication of cultured human melanoma cells by immune interferon and leukocytes. J. Natl. Cancer Inst. 73, 1067–1073.

    PubMed  CAS  Google Scholar 

  62. Fisher, P. B., Miranda, A. F., and Babiss, L. E. (1986) Measurement of the effect of interferons on cellular differentiation in murine and human melanoma cells. Methods Enzymol. 119, 611–618.

    Article  PubMed  CAS  Google Scholar 

  63. Garbe, C., Krasagakis, K., Zouboulis, C. C., Schroder, K., Kruger, S., Stadler, R., and Orfanos, C. E. (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, 231s–237s.

    Article  PubMed  CAS  Google Scholar 

  64. Zouboulis, C. C., Garbe, C., Kruger, S., and Orfanos, C. E. (1990) 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.

    Google Scholar 

  65. Krasagakis, K., Garbe, C., Kruger, S., and Orfanos, C. E. (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.

    Article  PubMed  CAS  Google Scholar 

  66. Chakraborty, N. G. and Mukherji, B. (1998) Human melanoma-specific, noncytolytic CD8+ T cells that can synthesize type I cytokine. Cancer Res. 58, 1363–1366.

    PubMed  CAS  Google Scholar 

  67. Bennicelli, J. L., Elias, J., Kern, J., and Guery, D. (1989) Production of interleukin 1 activity by cultured human melanoma cells. Cancer Res. 49, 930–935.

    PubMed  CAS  Google Scholar 

  68. Burrows, F. J., Haskard, D. O., and Bart, I. R. (1993) Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions. Cancer Res. 51, 4768–4775

    Google Scholar 

  69. Kock, A., Schwarz, T., Urbanski, A., Peng, Z., Vetterlein, M., Micksche, M., Ansel, J. C., Kung, H. F., and Luger, T. A. (1989) Expression and release of interleukin-1 by different human melanoma cell lines. J. Natl. Cancer Inst. 81, 36–42.

    Article  PubMed  CAS  Google Scholar 

  70. Lachman, L. B., Dinarello, C. A., Llansa, N. D., and Fidler, I. J. (1986) Natural and recombinant human interleukin 1-β is cytotoxic for human melanoma cells. J. Immunol. 136, 3098–3102.

    PubMed  CAS  Google Scholar 

  71. Nakai, S., Mizuno, K., Kaneta, M., and Hirai, Y. (1988) A simple, sensitive bioas-say for the detection of interleukin-1 using human melanoma A375 cell line. Biochem. Biophys. Res. Commun. 154, 1189–1196.

    Article  PubMed  CAS  Google Scholar 

  72. Mortarini, R., Belli, F., Parmiani, G., and 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.

    Article  PubMed  CAS  Google Scholar 

  73. Swope, V. B., Abdel-Malek, Z., Kassem, L. M., and Nordlund, J. J. (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.

    Article  PubMed  CAS  Google Scholar 

  74. Robertson, B., Gahring, L., Newton, R., and 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 

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

    PubMed  CAS  Google Scholar 

  76. Douvdevani, A., Huleihel, M., Zoller, M., Segal, S., and Apte, R. N. (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 

  77. Vile, R. G. and Hart, I. R. (1994) Targeting of cytokine gene expression to malignant melanoma cells using tissue specific promoter sequences. Ann. Oncol. 5(Suppl. 4), s59–s65.

    Google Scholar 

  78. Morinaga, Y., Suzuki, H., and 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 

  79. Lu, C., Vickers, M. F., and Kerbel, R. S. (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.

    Article  PubMed  CAS  Google Scholar 

  80. Armstrong, C. A., Murray, N., Kennedy, M., Koppula, S. V., Tara, D., and Ansel, J. C. (1994) Melanoma-derived interleukin 6 inhibits in vivo melanoma growth. J. Invest. Dermatol. 102, 278–284.

    Article  PubMed  CAS  Google Scholar 

  81. Lu, C. and Kerbel, R. S. (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 

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

    Article  PubMed  CAS  Google Scholar 

  83. Lotz, M., Jirik, F., Kabouridis, R., Tsoukas, C., Hirano, T., Kishimoto, T., and Carson, D. A. (1988) BSF-2/IL-6 is a costimulant for human thymocytes and T lymphocytes. J. Exp. Med. 167, 1253–1258.

    Article  PubMed  CAS  Google Scholar 

  84. Lee, C., Biondi, A., Wang, X. H., Iscove, N. N., de Sousa, J., Aarden, L. A., Wong, G. G., Clark, S. C., Messner, H. A., and Minden, M. D. (1989) A possible autocrine role for interleukin-6 in two lymphoma cell lines. Blood 74, 798–804.

    Google Scholar 

  85. Kawano, M., Hirano, T., Matsuda, P., Taga, T., Hurii, Y., Iwato, K., Asaoku, H., Tang, B., Tanabe, O., Tanale, H., Kuramoto, A., and Kishimoto, T. (1988) Autocrine generation and general requirement of BSF-2/IL-6 for human multiple myelomas. Nature 332, 83–85.

    Article  PubMed  CAS  Google Scholar 

  86. Kishimoto, T. (1989) The biology of interleukin-6. Blood 74, 1–10.

    PubMed  CAS  Google Scholar 

  87. Mule, J. J., McIntosh, J. K., Jablons, D. M., and Rosenberg, S. A. (1990) Antitu-mor activity of recombinant interleukin 6 in mice. J. Exp. Med. 17, 629–636.

    Article  Google Scholar 

  88. Sun, W. H., Kreisle, R. A., Phillips, A. W., and Ershler, W. B. (1992) In vivo and in vitro characteristics of interleukin 6-transfected B16 melanoma cells. Cancer Res. 52, 5412–5415.

    PubMed  CAS  Google Scholar 

  89. Kobayashi, M., Fitz, L., Ryan, M., Hewick, R. M., Clark, S. C., Chang, S., Loudon, R., Sherman, F., Perussia, B., and Trinchieri, G. (1989) Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J. Exp. Med. 170, 827–845.

    Article  PubMed  CAS  Google Scholar 

  90. Stern, A. S., Podlaski, F. J., Hulmes, J. D., Pan, Y. C. E., Quinn, P. M., Wolitzky, A.G., Familletti, P. D., Stremlo, D. L., Truitt, T., Chizzonite, R., and Gately, M. K. (1990) Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc. Natl. Acad. Sci. USA 87, 6808–6812.

    Article  PubMed  CAS  Google Scholar 

  91. Tahara, H., Zeh, H. J., Storkus, W. J., Pappo, I., Watkins, S. C., Gubler, U., Wolf, S. F., Robbins, P. D., and Lotze, M. T. (1994) Fibroblasts genetically engineered to secrete interleukin 12 can suppress tumor growth and induce antitumor immunity to a murine melanoma in vivo. Cancer Res. 54, 182–189.

    PubMed  CAS  Google Scholar 

  92. Grabstein, K. H., Eisenman, J., Shanebeck, K., et al. (1994) Cloning of a T cell growth factor that interacts with the β-chain of the interleukin-2 receptor. Science 264, 965–968.

    Article  PubMed  CAS  Google Scholar 

  93. Meazza, R., Verdiani, S., Biassoni, R., Coppolecchia, M., Gaggero, A., Orengo, A. M., Colombo, M. P., Azzarone, B., and Ferrini, S. (1996) Identification of a novel interleukin-15 (IL-15) transcript isoform generated by alternative splicing in human small cell lung cancer cell lines. Oncogene 12, 2187–2192.

    PubMed  CAS  Google Scholar 

  94. Onu, A., Pohl, T., Krause, H., and Bulfone-Paus, S. (1997) Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms. J. Immunol. 158, 255–262.

    PubMed  CAS  Google Scholar 

  95. Azzarone, B., Pottin-Clemenceau, C., Krief, P., Rubinstein, E., Jasmin, C., Scudeletti, M., and Indiveri, F. (1996) Are interleukin-2 and interleukin-15 tumor promoting factors for non-hematopoietic cells? Eur. Cytokine Network 7, 27–36.

    CAS  Google Scholar 

  96. Lugassy, C. and Escade, J. P. (1991) Immunolocation of TNF-α/cachectin in human melanoma cells: studies on co-cultivated malignant melanoma. J. Invest. Dermatol. 96, 238–242.

    Article  PubMed  CAS  Google Scholar 

  97. Zouboulis, C. C., Schroder, K., Garbe, C., Krasagakis, K., Kruger, S., and Orfanos, C. E. (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 

  98. Blankenstein, T., Qin, Z., Uberla, K., Muller, W., Rosen, H., Volk, H.-D., and 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 

  99. Qin, Z., Kruger-Krasagakes, S., Kunzendorf, U., Hock, H., Diammantstein, T., and 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 

  100. Shiku, H., Takahaski, T., Resnick, L. A., Oettgen, H. F., and Old, L. J. (1977) Cell surface antigens of human malignant melanoma. II. Recognition of autoan-tibodies with unusual characteristics. J. Exp. Med. 145, 784–789.

    Article  PubMed  CAS  Google Scholar 

  101. Houghton, A. N., Eisinger, M., Albino, A. P., Cairncross, J. G., and Old, L. J. (1982) Surface antigens of melanocytes and melanomas: markers of melanocyte differentiation and melanoma subsets. J. Exp. Med. 156, 1755–1766.

    Article  PubMed  CAS  Google Scholar 

  102. Foon, K. A., Sherwin, S. A., Abrams, P. G., et al. (1985) A phase I trial of recombinant gamma interferon in patients with cancer. Cancer Immunol. Immunother. 20, 193–197.

    Article  PubMed  CAS  Google Scholar 

  103. Kurzrock, R., Rosenblum, M. G., Sherwin, S. A., et al. (1985) Pharmacokinet-ics, single-dose tolerance, and biological activity of recombinant γ-interferon in cancer patients. Cancer Res. 45, 2866–2872.

    PubMed  CAS  Google Scholar 

  104. Kleinerman, E. S., Kurzrock, R., Wyatt, D., Quesada, J. R., Gutterman, J. U., and Fidler, I. J. (1986) Activation or suppression of the tumoricidal properties of monocytes from cancer patients following treatment with human recombinant γ-interferon. Cancer Res. 46, 5401–5405.

    PubMed  CAS  Google Scholar 

  105. Meyskens, F. L., Kopecky, K. J., Taylor, C. W., Noyes, R. D., Tuthill, R. J., Hersh, E. M., Feun, L. G., Doroshow, J. H., Flaherty, L. E., and Sondak, V. K. (1995) Randomized trial of adjuvant human interferon gamma versus observation in high-risk cutaneious melanoma: a Southwest Oncology Group Study. J. Natl. Cancer Inst. 87, 1710–1713.

    Article  PubMed  Google Scholar 

  106. Sondak, V. K. and Wolfe, J. A. (1997) Adjuvant therapy for melanoma. Curr. Opin. Oncol. 9, 189–204.

    Article  PubMed  CAS  Google Scholar 

  107. Pehamberger, H., Soyer, H. P., Steiner, A., Kofler, R., Binder, M., Mischer, P., Pachinger, W., Aubock, J., Fritsch, P., Kerl, H., and Wolff, K. (1998) Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. J. Clin. Oncol. 16, 1425–1429.

    PubMed  CAS  Google Scholar 

  108. Kirkwood, J. M., Strawderman, M. H., Ernstoff, M. S., Smith, T. J., Borden, E. C., and Blum, R. H. (1996) Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group trial EST 1684. J. Clin. Oncol. 14, 7–17.

    PubMed  CAS  Google Scholar 

  109. Kirkwood, J. M., Ibrahim, J., Sondak, V., Ernstoff, M., Flaherty, L., Smith, T., Richards, J., Rao, U., and Blum, R. (1999) Preliminary analysis of the E1690/ S9111/C9190 intergroup postoperative adjuvant trial of high-and low-dose IFNa2b (HDI and LDI) in high-risk primary or lymph node metastatic melanoma. Proc. Am. Soc. Clin. Oncol. 17, A2072.

    Google Scholar 

  110. Hill, G. J. II, Krementz, E. T., and Hill, H. Z. (1984) Dimethyl triazeno imida-zole carboxamide and combination therapy for melanoma: IV. Late results after complete response to chemotherapy (Central Oncology Group protocols 7130, 7131, and 7131A). Cancer 53, 1299–1305.

    Article  PubMed  Google Scholar 

  111. McClay, E. F., Mastrangelo, M. J., Berd, D., et al. (1992) Effective combination chemo/hormonal therapy for malignant melanoma: experience with three clinical trials. Int. J. Cancer 50, 553–556.

    Article  PubMed  CAS  Google Scholar 

  112. Falkson, C. I., Falkson, G., and Falkson, H. C. (1991) Improved results with the addition of interferon alpha-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J. Clin. Oncol. 9, 1403–1408.

    PubMed  CAS  Google Scholar 

  113. Thompson, D., Adena, M., and McLeod, G. R. C. (1993) Interferon alfa-2a does not improve response or survival when combined with dacarbazine in metastatic malignant melanoma: results of a multi-institutional Australian randomized trial, QMP8704. Melanoma Res. 3, 133–138.

    Article  Google Scholar 

  114. Bajetta, E., Di Leo, A., Zampino, M., et al. (1994) Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2A in the treatment of advanced melanoma. J. Clin. Oncol. 12, 806–811.

    PubMed  CAS  Google Scholar 

  115. Kirkwood, J. M., Ernstoff, M. S., Giuliano, A., et al. (1990) Interferon-2a and dacarbazine in melanoma. J. Natl. Cancer Inst. 82, 1062–1063.

    Article  PubMed  CAS  Google Scholar 

  116. Rusthoven, J. J., Quirt, I. C., Iscoe, N. A., et al. (1996) Randomized, double-blind placebo-controlled trial comparing the response rates of carmustine, dacarbazine and cisplatin with and without tamoxifen in patients with metastatic melanoma: National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol. 14, 2083–2090.

    PubMed  CAS  Google Scholar 

  117. Falkson, C. I., Ibrahim, J., Kirkwood, J., Coates, A. S., Atkins, M. B., and Blum, R. H. (1998) Phase III trial of dacarbazine versus dacarbazine with interferon-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study. J. Clin. Oncol. 16, 1743–1751.

    PubMed  CAS  Google Scholar 

  118. Atkins, M. B. (1998) The role of cytotoxic chemotherapeutic agents either alone or in combination with biological response modifiers, in Molecular Diagnosis, Prevention & Therapy of Melanoma (Kirkwood, J. M., ed.), Marcel Dekker, New York, pp. 219–251.

    Google Scholar 

  119. Rosenberg, S. A., Lotze, M. T., Muul, L. M., et al. (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N. Engl. J. Med. 313, 1485–1492.

    Article  PubMed  CAS  Google Scholar 

  120. Rosenberg, S. A., Lotze, M. T., Muul, L. M., et al. (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N. Engl. J. Med. 316, 889–897.

    Article  PubMed  CAS  Google Scholar 

  121. Atkins, M. B., Lotze, M. T., Dutcher, J. P., et al. (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J. Clin. Oncol. 17, 2105–2116.

    PubMed  CAS  Google Scholar 

  122. Atkins, M. B., O′Boyle, K. R., Sosman, J. A., et al. (1994) Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma. J. Clin. Oncol. 12, 1553–1560.

    PubMed  CAS  Google Scholar 

  123. Keilholz, U., Conradt, C., Legha, S. S., et al. (1998) Results of interleukin-2-based treatment in advanved melanoma: a case record-based analysis of 631 patients. J. Clin. Oncol. 16, 2921–2929.

    PubMed  CAS  Google Scholar 

  124. Legha, S. S., Ring, S., Eton, O., Bedikian, A., Buzaid, A. C., Plager, C., and Papadopoulos, N. (1998) Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J. Clin. Oncol. 16, 1752–1759.

    PubMed  CAS  Google Scholar 

  125. McDermott, D. F., Trehu, E. G., Mier, J. W., Sorce, D., Rand, W., Ronayne, L., Kappler, K., Clancy, M., Klempner, M., and Atkins, M. B. (1998) A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor. Clin. Cancer Res. 5, 1203–1213.

    Google Scholar 

  126. Richards, J. M., Gale, D., Mehta, N., and Lestingi, T. (1999) Combination of chemotherapy with interleukin-2 and interferon alfa for the treatment of metastatic melanoma. J. Clin. Oncol. 17, 651–657.

    PubMed  CAS  Google Scholar 

  127. Bajetta, E., Vecchio, M. D., Mortarini, R., Nadeau, R., Rakhit, A., Rimassa, L., Fowst, C., Borri, A., Anichini, A., and Parmiani, G. (1998) Pilot study of subcutaneous recombinant human interleukin 12 in metastatic melanoma. Clin. Cancer Res. 4, 75–85.

    PubMed  CAS  Google Scholar 

  128. Chachoua, A., Oratz, R., Liebes, L., Alter, R. S., Felice, A., Peace, D., Vilcek, J., and Blum, R. H. (1994) Phase Ib trial of granulocyte-macrophage colony-stimulating factor combined with murine monoclonal antibody R24 in patients with metastatic melanoma. J. Immunother. 16, 132–141.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Humana Press Inc.

About this protocol

Cite this protocol

Clark, J.I. (2001). Role of Cytokines in Pathology of Melanoma and Use of Biologic Response Modifiers in Melanoma. In: Nickoloff, B.J., Hood, L. (eds) Melanoma Techniques and Protocols. Methods in Molecular Medicine, vol 61. Humana Press. https://doi.org/10.1385/1-59259-145-0:241

Download citation

  • DOI: https://doi.org/10.1385/1-59259-145-0:241

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-684-0

  • Online ISBN: 978-1-59259-145-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics