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Role of interleukin-6 in the proliferation of human multiple myeloma cell
lines OCI-My 1 to 7 established from patients with advanced stage of the
disease
JK Hitzler, H Martinez-Valdez, DB Bergsagel, MD Minden and HA Messner
Ontario Cancer Institute, Toronto, Canada.
Interleukin-6 (IL-6) has been shown to stimulate the proliferation of
multiple myeloma cells purified to a high degree from human bone marrow.
IL-6 production in multiple myeloma has been attributed to cells belonging
to the myeloma clone, thus supporting a mechanism of autostimulation. In
addition, it has been shown that IL-6 may be produced by auxiliary cell
populations of the bone marrow that are not part of the myeloma clone. A
definitive separation of both putative sources for IL-6 may be difficult to
achieve in fresh patient IL-6 growth requirement and production by pure
myeloma cell populations using seven human myeloma cell lines (OCI-My 1 to
7) that were established from patients with advanced disease. The
proliferative response of each line to recombinant IL-6 was measured in a
clonogenic assay providing human plasma and methylcellulose as a viscous
support and by 3H-thymidine uptake in liquid suspension culture. We
observed marked heterogeneity, ranging from IL-6-dependent colony formation
by OCI-My 4, to IL-6-independent growth. All lines expressed mRNA for the
IL-6 receptor. Expression of IL-6 mRNA was analyzed after amplification by
polymerase chain reaction and was present in five of seven lines. IL- 6
protein was detected by enzyme-linked immunosorbent assay (ELISA) in the
culture supernatants of two lines (OCI-My 3 and 2). Its functional activity
was confirmed in a bioassay using the IL-6-dependent murine hybridoma line
B 13.29. This activity was neutralized by anti-IL-6 antibody. Two lines did
not express mRNA for IL-6. The remaining three lines expressed mRNA for
IL-6, but did not secrete IL-6 protein. Immunoprecipitation experiments
with lysates of one of these three lines did not detect the presence of
IL-6 protein. These results suggest that autocrine stimulation by IL-6 may
occur in some cell lines derived from patients with multiple myeloma.
However, it does not represent a universal mechanism in myeloma cell
growth.
Volume 78,
Issue 8,
pp. 1996-2004,
10/15/1991
Copyright © 1991 by The American Society of Hematology
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