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-1 0 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, 199 5). Because the IL-10 receptor does not involve the gp130 IL-6 transdu cer, we have attempted to elucidate the mechanisms of IL-10 action on myeloma cells. Our results indicate that the myeloma cell growth facto r activity of IL-10 was abrogated by an antibody to the gp130 IL-6 tra nsducer, indicating that it was mediated through one of the gp130-acti vating 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) c onstitutively but failed to produce IL-6, IL-11 and leukemia-inhibitor y 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 in ducing 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 patie nts. 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 O M 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 togeth er, these results show that IL-10 is a key cytokine for inducing the e xpression of LIFR and IL-11R and possibly another uncharacterized OM c oreceptor on myeloma cells and that OM and IL-10 might be produced by myeloma cells. They also emphasize that all myeloma cell growth factor s reported to date involve an activation of the gp130 IL-6 transducer. (C) 1996 by The American Society of Hematology.