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  • Original Article
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Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases

Oncogene volume 26, pages 4987–4998 (2007)Cite this article

Abstract

An acidic domain (AD) of gp130 was previously found to interact with the Src family kinase (SFK) Hck. Here, the influence of myristoylated peptides derived from this AD was assessed in the mouse myeloma cell line, 7TD1. The IL-6-dependent growth of 7TD1 cells was reduced by ∼75%, if 100 μ M of myristoylated 18mer peptide (18AD) was included in the growth medium, but was unaffected by a control peptide with scrambled sequence (18sc). A similar differential inhibition by peptides 18AD and 18sc was observed for the erythropoietin-dependent growth of BaF-EH cells expressing chimeric erythropoietin receptor-gp130 and human Hck and for the human myeloma cell line INA-6. While the peptide 18AD concentration inhibiting 50% was ∼30 μ M in 7TD1 and BaF-EH cells, peptide 18AD did not significantly inhibit growth of IL-6-independent MM1.S myeloma and OKT1 hybridoma cells or of BaF-EH cells supplied with IL-3. Treatment with 100 μ M peptide 18AD caused the same degree or 60% of apoptosis induction as IL-6 deprivation in 7TD1 or INA-6 cells, respectively. Co-immunoprecipitation experiments revealed that peptide 18AD interfered with the association of Hck and gp130 in 7TD1 lysates in a concentration-dependent manner. IL-6-treatment of INA-6 cells induced the kinase activities of Fyn, Lyn and Hck, but not Src, and the IL-6-induced SFK activities were inhibited by peptide 18AD. Expression in 7TD1 cells of a kinase-inactive Hck mutant (K269R) elicited a dominant-negative effect on cell number increases providing further evidence that SFKs are required for gp130 signalling in myeloma cells.

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Acknowledgements

We thank Drs Christine Mayr and Thomas Fröhlich for expert advice on FACS analysis and peptide labeling, respectively. This work was supported by grants of the Deutsche Krebshilfe (10–1678-Ha2) and Deutsche Forschungsgemeinschaft (Ha-1680/7–1, 7–2), and a fellowship of the German José Carreras Leukaemia Foundation (DJCLS-F05/04) to AH. RT was supported by the Portuguese Foundation for Science and Technology and the European Social Fund.

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Authors and Affiliations

  1. Clinical Cooperation Group Gene Therapy, GSF – National Research Center for Environment and Health, Munich, Germany

    A Hausherr, R Tavares, O Mitina, M Hallek & G Krause

  2. SIREEN AG, Am Klopferspitz, Martinsried, Germany

    M Schäffer, A Obermeier & C Miksch

  3. CRELUX GmbH, Am Klopferspitz, Martinsried, Germany

    M Schäffer

  4. Institute of Molecular Immunology, GSF – National Research Center for Environment and Health, Munich, Germany

    J Ellwart

  5. Clinic I for Internal Medicine, University Hospital Cologne, Cologne, Germany

    M Hallek & G Krause

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Correspondence to G Krause.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Hausherr, A., Tavares, R., Schäffer, M. et al. Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases. Oncogene 26, 4987–4998 (2007). https://doi.org/10.1038/sj.onc.1210306

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