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.
Article|
April 01 1994
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.
X G Zhang,
X G Zhang
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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J J Gu,
J J Gu
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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Z Y Lu,
Z Y Lu
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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K Yasukawa,
K Yasukawa
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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G D Yancopoulos,
G D Yancopoulos
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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K Turner,
K Turner
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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M Shoyab,
M Shoyab
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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T Taga,
T Taga
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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T Kishimoto,
T Kishimoto
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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R Bataille
R Bataille
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
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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.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 179 (4): 1337–1342.
Citation
X G Zhang, J J Gu, Z Y Lu, K Yasukawa, G D Yancopoulos, K Turner, M Shoyab, T Taga, T Kishimoto, R Bataille; 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.. J Exp Med 1 April 1994; 179 (4): 1337–1342. doi: https://doi.org/10.1084/jem.179.4.1337
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