Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130.

DOI PDF 被引用文献5件
  • X G Zhang
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • J J Gu
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • Z Y Lu
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • K Yasukawa
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • G D Yancopoulos
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • K Turner
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • M Shoyab
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • T Taga
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • T Kishimoto
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
  • R Bataille
    Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.

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<jats:p>Interleukin 6 (IL-6) is a major growth factor for tumor plasma cells involved in human multiple myeloma (MM). In particular, human myeloma cell lines (HMCL), whose growth is completely dependent on addition of exogenous IL-6, can be obtained reproducibly from every patient with terminal disease. Four cytokines, ciliary neurotropic factor (CNTF), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OM), use the same transducer chain (signal transducer gp130) as IL-6 and share numerous biological activities with this IL. We found that these four cytokines stimulated proliferation and supported the long-term growth of two out of four IL-6-dependent HMCL obtained in our laboratory. Half-maximal proliferation was obtained with cytokine concentrations ranging from 0.4 to 1.2 ng/ml for IL-11, LIF, and OM. CNTF worked at high concentrations only (90 ng/ml), but addition of soluble CNTF receptor increased sensitivity to CNTF 30-fold. The growth-promoting effect of these four cytokines was abrogated by anti-gp130 antibodies, contrary to results for anti-IL-6 receptor or anti-IL-6 antibodies. No detectable changes in the morphology and phenotype were found when myeloma cells were cultured with one of these four cytokines instead of IL-6. Concordant with their IL-6-dependent growth, the four HMCL expressed membrane IL-6R and gp130 detected by FACS analysis. LIF-binding chain gene (LIFR) was expressed only in the two HMCL responsive to LIF and OM.</jats:p>

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