Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop.
We have a previously reported that interleukin-10 (IL-10) is a potent but IL-6-unrelated growth factor for freshly explanted myeloma cells (Lu et al, Blood 85:2521, 1995). We have also shown that exogenous IL-10 supported the growth of XG-1 and XG-2 human myeloma cell lines (HMCL) through an IL-6-independent mechanism. (Lu et al, Blood 85:2521, 1995). Because the IL-10 receptor does not involve the gp 130 IL-6 transducer, we have attempted to elucidate the mechanisms of IL-10 action on myeloma cells. Our results indicate that the myeloma cell growth factor activity of IL-10 was abrogated by an antibody to the gp 130 IL-6 transducer, indicating that it was mediated through one of the gp 130-activating cytokines. We found that myeloma cells from XG-1 and XG-2 HMCL and from 5 of 6 patients' tumoral samples produced oncostatin M (OM) constitutively but failed to produce IL-6, IL-11 and leukemia-inhibitory factor (LIF). The autocrine OM was inactive in the absence of IL-10 due to lack of a functional OM receptor on myeloma cells. IL-10, by inducing the receptor for LIF (LIFR), produced a functional autocrine OM loop in XG-1 and XG-2 cells and in primary myeloma cells from 2 patients. We also found that some myeloma cell lines (XG-4, XG-6, and XG-7) an fresh myeloma cells from 3 of 6 patients produced an autocrine IL-10 and that these cells constitutively expressed LIFR. One HMCL (XG-7) produced IL-10, OM, and IL-6 an expressed LIFR. The XG-7 cells used OM and IL-6 as autocrine growth factors. We have previously shown that IL-10 could induce IL-11 receptor in myeloma cells and confer on them sensitivity to IL-11 (Lu et al, FEBS Lett 377:515, 1995). Taken together, these results show that IL-10 is a key cytokine for inducing the expression of LIFR and IL-11R and possibly another uncharacterized OM coreceptor on myeloma cells and that OM and IL-10 might be produced by myeloma cells. They also emphasize that all myeloma cell growth factors reported to data involve an activation of the gp130 IL-6 transducer.
Institute for Molecular Genetics, Montpellier, France.
Z J
ZJ
Gu
V
V
Costes
Z Y
ZY
Lu
X G
XG
Zhang
V
V
Pitard
J F
JF
Moreau
R
R
Bataille
J
J
Wijdenes
J F
JF
Rossi
B
B
Klein
D015703:Antigens, CD / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D017370:Interleukin-11 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000502:physiology; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000502:physiology; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053683:Oncostatin M; D010452:Peptide Biosynthesis; D010455:Peptides / Q000502:physiology*; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000235:genetics; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D015703:Antigens, CD; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D016753:Interleukin-10; D050822:Cytokine Receptor gp130