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: 10.1084/jem.179.4.1337
• Publication Date: 2004-06-24T07:56:10Z
• Authors: X G Zhang; J J Gu; Z Y Lu; K Yasukawa; G D Yancopoulos; K Turner; M Shoyab; T Taga; T Kishimoto; R Bataille
• Keywords: 0301 basic medicine; Lymphokines; Membrane Glycoproteins; Interleukin-6; Nerve Tissue Proteins; Oncostatin M; Interleukin-11; Leukemia Inhibitory Factor; Growth Inhibitors; 03 medical and health sciences; Antigens, CD; Cytokine Receptor gp130; Tumor Cells, Cultured; Humans; Receptors, Growth Factor; Ciliary Neurotrophic Factor; Growth Substances; Multiple Myeloma; Peptides; Receptor, Ciliary Neurotrophic Factor; Signal Transduction

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.