Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop

Z. J. Gu , V. Costes (1, 2) , Z. Y. Lu , X. G. Zhang (3) , V. Pitard , J. F. Moreau , R. Bataille (4) , J. Wijdenes , J. F. Rossi , B. Klein

1 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
2 Pathogénèse et contrôle des infections chroniques (PCCI)
3 School of Earth and Space Sciences [Beijing]
4 On behalf of the IFM group

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 gp130 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 gp130 IL-6 transducer, indicating that it was mediated through one of the gp130-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 date involve an activation of the gp130 IL-6 transducer. (C) 1996 by The American Society of Hematology.

Mots clés: leukemia inhibitory factor human multiple-myeloma signal transducer differentiation factor monoclonal-antibody expression cloning plasma-cells t-cells b-cells receptor

Domaines: Biochimie, Biologie Moléculaire

Z. J. Gu, V. Costes, Z. Y. Lu, X. G. Zhang, V. Pitard, et al.. Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop. Blood, 1996, 88 (10), pp.3972--3986. ⟨10.1182/blood.V88.10.3972.bloodjournal88103972⟩. ⟨hal-02194142⟩