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 inh ibitory factor (LIF), interleukin 6 (IL-6), IL-11, and the inhibitory effect of anti-IL-6 antibody (Ab), anti-IL-6 receptor monoclonal antib ody (mAb), and anti-gp130 mAb on the growth of human plasmacytoma cell s freshly isolated from a patient with multiple myeloma. The purified cells showed a plasmacytoid morphology and expressed CD38, CD54, and C D56 antigens but no CD3, CD5, CD10, CD19, CD20, or very late antigen 5 . IL-6 receptor (IL-6R) and its signal transducer, gp130, were express ed 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 [H-3]TdR incorporation in vitro. Both anti-IL-6 Ab and anti-IL-6R mAb inhibited the growth of the cells in the presence or ab sence of exogenous IL-6. These cells release IL-6 but not OSM or LIF i nto the culture supernatant during short-term culture. Therefore, an a utocrine growth mechanism mediated by IL-6, but not by OSM or LIF, was confirmed. Furthermore, anti-gp130 mAb completely inhibited the proli feration 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 p lasmacytoma cells through a common signal transducer, gp130, on their cell surface, and also suggest the potential therapeutic application o f anti-gp130 mAb, as well as anti-IL-6R mAb against myeloma/plasmacyto mas.