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.
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.
Zhang
X G
XG
Institute for Molecular Genetics, CNRS BP5051, Montepellier, France.
Gu
J J
JJ
Lu
Z Y
ZY
Yasukawa
K
K
Yancopoulos
G D
GD
Turner
K
K
Shoyab
M
M
Taga
T
T
Kishimoto
T
T
Bataille
R
R
D015703:Antigens, CD; D020934:Ciliary Neurotrophic Factor; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D017370:Interleukin-11 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D053683:Oncostatin M; D010455:Peptides / Q000502:physiology; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D020934:Ciliary Neurotrophic Factor; D006131:Growth Inhibitors; D006133:Growth Substances; C494199:IL6ST protein, human; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C508351:OSM protein, human; D010455:Peptides; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor; D053683:Oncostatin M; D050822:Cytokine Receptor gp130