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Characterization of an interleukin-6-mediated autocrine growth loop in the
human multiple myeloma cell line, U266
G Schwab, CB Siegall, LA Aarden, LM Neckers and RP Nordan
Tumor Cell Biology Section, National Cancer Institute, NIH, Bethesda, MD
20892.
It has been reported recently that freshly isolated human myeloma cell
cultures proliferate in response to added interleukin-6 (IL-6). Endogenous
levels of IL-6 found in the same cultures suggested that an autocrine
growth loop may contribute to cell growth. However, the lack of homogenous
cell populations in primary myeloma cultures has made it difficult to
distinguish between paracrine and autocrine growth mechanisms. To precisely
address the autocrine growth issue we have evaluated the growth of the
human myeloma cell line, U266. We have found that a neutralizing anti-IL-6
monoclonal antibody can inhibit U266 proliferation. Furthermore, the
addition of IL-6 antisense oligonucleotides also inhibits U266
proliferation. These effects are reversed by adding IL-6, suggesting the
presence of an autocrine loop. Using bioassays with two different
IL-6-dependent cell lines, we were able to detect IL-6 in concentrated U266
supernatants. IL-6 mRNA was detected by polymerase chain reaction
amplification of cDNA. Cell cycle parameter analysis shows that IL-6 acts
to release a block in G1. Taken together these results present conclusive
evidence for IL-6-mediated autocrine growth in the U266 human myeloma cell
line.
Volume 77,
Issue 3,
pp. 587-593,
02/01/1991
Copyright © 1991 by The American Society of Hematology
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