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Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive
to anti-Fas antibody resulting in apoptosis
Y Shima, N Nishimoto, A Ogata, Y Fujii, K Yoshizaki and T Kishimoto
Department of Medicine III, Osaka University Medical School, Japan.
To find out which cytokines are involved in the pathogenesis of multiple
myeloma, we investigated cytokine receptor expression on myeloma cells
using a panel of monoclonal antibodies (MoAbs). Flow cytometric analysis of
five myeloma cell lines (RPMI8226, ARH77, KMM-1, U266, and Hs) and myeloma
cells freshly isolated from eight patients showed that interleukin-1
receptor (IL-1R) type I and type II, IL-2R alpha and beta chains, IL-4R,
IL-6R, IL-7R, IL-8R, granulocyte macrophage colony-stimulating factor
receptor (GM-CSFR), c-kit (stem cell factor receptor [SCFR]), membrane
bound stem cell factor (MBSCF), and tumor necrosis factor (TNF) receptors
type I and type II were not always detected on the myeloma cells. However,
interferon-gamma receptor, gp130, and Fas antigen were constitutively
expressed, except one sample. To determine the role of Fas antigen on
myeloma cells, these cells were cultured with anti-Fas MoAb. Apoptotic
changes characterized by loss of cell volume, membrane blebbing,
fragmentation of nuclei, and condensed chromatin were observed in three of
five myeloma cell lines. When bcl-2 expression was examined, it was seen in
all the cell lines regardless of the sensitivity to anti-Fas MoAb.
Furthermore, anti-Fas MoAb not only induced apoptosis of freshly isolated
myeloma cells but also inhibited the DNA synthesis, although such effects
varied from patient to patient. The data indicate that only some myeloma
cells undergo apoptosis in response to the signal mediated by the Fas
antigen.
Volume 85,
Issue 3,
pp. 757-764,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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