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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2172-2178
NEOPLASIA
Requirements of src family kinase activity associated with
CD45 for myeloma cell proliferation by interleukin-6
Hideaki Ishikawa,
Naohiro Tsuyama,
Saeid Abroun,
Shangqin Liu,
Fu-Jun Li,
Osamu Taniguchi, and
Michio M. Kawano
From the Department of Bio-Signal Analysis, Applied
Medical Engineering Science, Graduate School of Medicine, Yamaguchi
University, Ube, Japan; and Otsuka Tokyo Assay Laboratories, Tokyo,
Japan.
Specific intracellular signals mediated by interleukin-6 (IL-6)
receptor complexes, such as signal transducer and activator of
transcription 3 (STAT 3) and extracellular signal-regulated kinase
(ERK) 1/2, are considered to be responsible for inducing a variety of
cellular responses. In multiple myeloma, IL-6 only enhanced the
proliferation of CD45+ tumor cells that harbored the
IL-6-independent activation of src family kinases even though STAT3
and ERK1/2 could be activated in response to IL-6 in both
CD45+ and CD45 cells. Furthermore, the
IL-6-induced proliferation of CD45+ U266 myeloma cells was
significantly suppressed by Lyn-specific antisense
oligodeoxynucleotides or a selective src kinase inhibitor. These
results indicate that the activation of both STAT3 and ERK1/2 is not
enough for IL-6-induced proliferation of myeloma cell lines that
require src family kinase activation independent of IL-6 stimulation. Thus, the activation of the src family kinases associated with CD45 expression is a prerequisite for the proliferation of myeloma
cell lines by IL-6. We propose a mechanism for IL-6-induced cell
proliferation that is strictly dependent upon the cellular context in myelomas.
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