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Inhibitory effect of all-trans retinoic acid on the growth of freshly
isolated myeloma cells via interference with interleukin-6 signal
transduction [see comments]
A Ogata, N Nishimoto, Y Shima, K Yoshizaki and T Kishimoto
Department of Medicine III, Osaka University Medical School, Japan.
We showed the dose-dependent growth inhibition by alltrans retinoic acid
(ATRA) of myeloma cells freshly isolated from patients. ATRA downregulated
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-gp 130 antibody in every sample. Furthermore,
ATRA inhibited the production of IL-6 from both myeloma cells and marrow
stromal cells, and recombinant IL-6 (rIL-6) could partially 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 myeloma cells and by the
inhibition of IL-6 production from myeloma and stromal 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 morphological change. The inhibitory
effect of ATRA on myeloma cell proliferation was observed in 10 of 14
samples obtained from eight patients, which suggests that ATRA may be a
potent new therapeutic agent for some myeloma patients.
Volume 84,
Issue 9,
pp. 3040-3046,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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