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Granulocyte-macrophage colony-stimulating factor synergizes with
interleukin-6 in supporting the proliferation of human myeloma cells [see
comments]
XG Zhang, R Bataille, M Jourdan, S Saeland, J Banchereau, P Mannoni and B Klein
Institut National de la Sante et de la Recherche Medicale, Montpellier,
France.
The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in
the growth of multiple myeloma (MM) was investigated in 21 patients with
MM. In 17 patients with proliferating myeloma cells in vivo, recombinant
GM-CSF significantly increased the endogenous-IL-6-mediated spontaneous
myeloma cell proliferation occurring in 5-day cultures of tumor cells in
vitro (P less than .01). Furthermore, GM-CSF was detected in 5-day culture
supernatants of myeloma bone marrow cells. This endogenous GM-CSF was
produced by the myeloma bone marrow microenvironment but not by myeloma
cells and contributed to the spontaneous myeloma-cell proliferation
observed in 5-day cultures. In fact, this proliferation was partially
blocked (67%) by anti-GM-CSF monoclonal antibodies. The stimulatory effect
of rGM-CSF was mediated through IL-6 because it was abrogated by anti-IL-6
monoclonal antibodies. rGM-CSF did not reproducibly increase the endogenous
IL-6 production in short-term cultures of bone marrow cells of MM patients.
Using an IL-6-dependent myeloma cell line (XG-1 cell line), rGM-CSF was
shown to act directly on myeloma cells stimulating by twofold their IL- 6
responsiveness. rGM-CSF did not induce any IL-6 production in XG-1 cells,
nor was it able to sustain their growth alone. Although no detectable
GM-CSF levels were found in the peripheral or bone marrow blood of MM
patients, it is possible that GM-CSF, produced locally by the tumoral
environment, enhances the IL-6 responsiveness of myeloma cells in vivo in a
way similar to that reported here in vitro.
Volume 76,
Issue 12,
pp. 2599-2605,
12/15/1990
Copyright © 1990 by The American Society of Hematology
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