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
| Autor: | T Taga, Zhao-Yang Lu, K Yasukawa, T Kishimoto, M Shoyab, R Bataille, J J Gu, G D Yancopoulos, Xue-Guang Zhang, K Turner |
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| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_treatment
Immunology Leukemia inhibitory factor receptor Nerve Tissue Proteins Oncostatin M Ciliary neurotrophic factor Leukemia Inhibitory Factor Antigens CD medicine Cytokine Receptor gp130 Tumor Cells Cultured Immunology and Allergy Humans Receptors Growth Factor Ciliary Neurotrophic Factor Interleukin 6 Growth Substances Receptor Ciliary Neurotrophic Factor Lymphokines Membrane Glycoproteins biology Interleukin-6 Growth factor Articles Glycoprotein 130 Interleukin-11 Growth Inhibitors Cytokine Cancer research biology.protein Multiple Myeloma Peptides Leukemia inhibitory factor Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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