Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130.
We analyzed the stimulatory effect of oncostatin M (OSM), leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and the inhibitory effect of anti-IL-6 antibody (Ab), anti-IL-6 receptor monoclonal antibody (mAb), and anti-gp130 mAb on the growth of human plasmacytoma cells freshly isolated from a patient with multiple myeloma. The purified cells showed a plasmacytoid morphology and expressed CD38, CD54, and CD56 antigens but no CD3, CD5, CD10, CD19, CD20, or very late antigen 5. IL-6 receptor (IL-6R) and its signal transducer, gp130, were expressed on their cell surface at a low level. Dose-dependent proliferation of the cells in response to OSM, LIF, and IL-6, but not to IL-11, was observed using [3H]TdR incorporation in vitro. Both anti-IL-6 Ab and anti-IL-6R mAb inhibited the growth of the cells in the presence or absence of exogenous IL-6. These cells release IL-6 but not OSM or LIF into the culture supernatant during short-term culture. Therefore, an autocrine growth mechanism mediated by IL-6, but not by OSM or LIF, was confirmed. Furthermore, anti-gp130 mAb completely inhibited the proliferation of the cells induced by OSM, LIF, as well as IL-6. These data indicate that OSM, LIF, and IL-6 can act as growth factors of human plasmacytoma cells through a common signal transducer, gp130, on their cell surface, and also suggest the potential therapeutic application of anti-gp130 mAb, as well as anti-IL-6R mAb against myeloma/plasmacytomas.
Nishimoto
N
N
Department of Medicine III, Osaka University Medical School, Japan.
Ogata
A
A
Shima
Y
Y
Tani
Y
Y
Ogawa
H
H
Nakagawa
M
M
Sugiyama
H
H
Yoshizaki
K
K
Kishimoto
T
T
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001859:Bone Neoplasms / Q000473:pathology; D002455:Cell Division; D050822:Cytokine Receptor gp130; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D017370:Interleukin-11 / Q000502:physiology; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology; D053683:Oncostatin M; D010455:Peptides / Q000502:physiology*; D010954:Plasmacytoma / Q000276:immunology / Q000473:pathology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008562:Membrane Glycoproteins; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D050822:Cytokine Receptor gp130