INHIBITORY EFFECT OF ALL-TRANS-RETINOIC ACID ON THE GROWTH OF FRESHLYISOLATED MYELOMA CELLS VIA INTERFERENCE WITH INTERLEUKIN-6 SIGNAL-TRANSDUCTION

We showed the dose-dependent growth inhibition by all-trans retinoic a cid (ATRA) of myeloma cells freshly isolated from patients. ATRA downr egulated the cell surface expression of interleukin-6 receptor (IL-6R) and/or glycoprotein (gp) 130. The growth-inhibitory activity of ATRA was well correlated with that of anti-gp130 antibody in every sample. Furthermore, ATRA inhibited the production of IL-6 from both myeloma c ells and marrow stromal cells, and recombinant IL-6 (rIL-6) could part ially recover the myeloma cell growth that had been inhibited by ATRA. These data suggest that ATRA may inhibit the proliferation of myeloma cells both by the downregulation of IL-6R and gp130 expression on mye loma cells and by the inhibition of IL-6 production from myeloma and s tromal cells. Prednisolone (PSL) and interferon-gamma (IFN-gamma) also inhibited the myeloma growth, while their effects were different from those of ATRA on IL-6 R and gp130 expression, IL-6 production, and mo rphological change. The inhibitory effect of ATRA on myeloma cell prol iferation was observed in 10 of 14 samples obtained from eight patient s, which suggests that ATRA may be a potent new therapeutic agent for some myeloma patients. (C) 1994 by The American Society of Hematology.