Cytokine-mediated growth inhibition of human melanoma cells

  • Marcin Kortylewski
  • Peter C. Heinrich
  • Andrzej Mackiewicz
  • Iris Behrmann
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 495)


Interleukin-(IL)-6 and oncostatin M (OSM), closely related cytokines sharing gp130 as a common receptor signal transducing subunit’, are known for their antiproliferative action on melanocytes2and melanoma cells from early phases of tumor growth34. In contrast, cells from advanced stage melanomas in most cases acquire a so called “multicytokine resistance” phenotype becoming unresponsive to several cytokines including IL-6 and/or OSM. Therefore, it seems plausible that local paracrine growth inhibition plays an important role for the prevention of the firstin situstages of melanoma development. We and others suggest that in the case of melanoma cells Jak/STAT signaling can be critical for the negative regulation of their growths6


A375 Cell Melanoma Cell Human Melanoma Cell Human Melanoma Cell Line Chimeric Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Heinrich, P.C., Behrmann, I., G, M.-N., Schaper, F., Graeve, L.,1998, Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway.Biochem J334:297–314.PubMedGoogle Scholar
  2. 2.
    Swope, V.B., Abdel-Malek, Z., Kassem, L.M., Nordlund, J.J.,1991, Interleukinsla and 6 and tumor necrosis factor-a are paracrine inhibitors of human melanocyte proliferation and melanogenesis.J Invest Dermatol96:180–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Lu, C., Vickers M. F., 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. USA89:9215–9219.PubMedCrossRefGoogle Scholar
  4. 4.
    Lu, C., Rak J. W., Kobayashi H., Kerbel R. S., 1993, Increased resistance to oncostatin M-induced growth inhibition of human melanoma cell lines derived from advanced-stage lesions.Cancer Res.53:2708–2711.PubMedGoogle Scholar
  5. 5.
    Oh, J.-W., Katz A., Haroch S., Eisenbach L., Revel M., Chebath J., 1997, Unmasking by soluble IL-6 receptor of IL-6 effect on metastatic melanoma: growth inhibition and differentiation of B16–F10.9 tumor cells.Oncogene15:569–577.PubMedCrossRefGoogle Scholar
  6. 6.
    Kortylewski, M., Heinrich, P. C., Mackiewicz, A., Schniertshauer, U., Klingmuller, U., Nakajima, K., Hirano, T., Horn, F., Behrmann, I., 1999, Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kipl.Oncogene18:3742–53.PubMedCrossRefGoogle Scholar
  7. 7.
    Gerhartz, C., Heesel, B., Sasse, J., Hemmann, U., Landgraf, C., Schneider-Mergener, J., Horn, F., Heinrich, P.C., Graeve, L., 1996, Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130.JBiol Chem271:12991–8.CrossRefGoogle Scholar
  8. 8.
    Nakajima, K., Yamanaka, Y., Nakae, K., Kojima, H., Ichiba, M., Kiuchi, N., Kitaoka, T., Fukada, T., Hibi, M., Hirano, T., 1996, A central role for Stat3 in IL-6-induced regulation of growth and differentiation in MI leukemia cells.Embo J15:3651–8.PubMedGoogle Scholar
  9. 9.
    Sherr C.J., Roberts.J.M., 1999, CDK inhibitors: positive and negative regulators of G1-phase progression.Genes Dev13:1501–1512.PubMedCrossRefGoogle Scholar
  10. 10.
    Florenes, V.A., Maelandsmo, G.M., Kerbel, R.S., Slingerland, J.M., Nesland, J.M., Holm, R., 1998, Protein expression of the cell-cycle inhibitor p27Kipl in malignant melanoma: inverse correlation with disease-free survival.Am J Pathol153:305–12..PubMedCrossRefGoogle Scholar
  11. 11.
    Worm J., Bartkova J., Kirkin A.F., Straten P., Zeuthen J., Bartek J., Guldberg P., 2000, Aberrant p27K1P1promoter methylation in malignant melanoma.Oncogene19:5111–5115.PubMedCrossRefGoogle Scholar
  12. 12.
    Ball, N. J., Yohn, J. J., Morelli, J. G., Norris, D. A., Golitz, L. E., Hoeffler, J. P.,1994, Ras mutations in human melanoma: a marker of malignant progression.J Invest Dermatol102:285–90.CrossRefGoogle Scholar
  13. 13.
    Jafari, M., Papp, T., Kirchner, S., Diener, U., Henschler, D., Burg, G., Schiffmann, D., 1995, Analysis of ras mutations in human melanocytic lesions: activation of the ras gene seems to be associated with the nodular type of human malignant melanoma.J Cancer Res Clin Oncol121:23–30.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Marcin Kortylewski
    • 1
    • 2
  • Peter C. Heinrich
    • 1
  • Andrzej Mackiewicz
    • 2
  • Iris Behrmann
    • 1
  1. 1.Department of BiochemistryRWTH AachenGermany
  2. 2.Department of Cancer Immunology at GreatPoland Cancer CenterUniversity School of Medical SciencesPoznanPoland

Personalised recommendations