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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3887-3897
Induction of CD45 Expression and Proliferation in U-266 Myeloma
Cell Line by Interleukin-6
Maged S. Mahmoud,
Hideaki Ishikawa,
Ryuichi Fujii, and
Michio M. Kawano
From the Department of Immuno-hematology, Yamaguchi University School
of Medicine, Ube, Japan.
Recently, there has been an increasing interest in the expression
pattern and biological significance of the CD45 molecule in myeloma
cells. In this study, we have further defined the phenotypic pattern of
CD45 expression on myeloma cells. Using a panel of myeloma cell lines,
we showed that CD45 showed a remarkably heterogeneous pattern of
expression. Whereas some cell lines were CD45+ and others
were CD45 , the U-266 cell line, although predominantly
CD45, still had a considerable subpopulation of
CD45+ cells. Among the myeloma cell lines examined, there
was a direct correlation between interleukin-6 (IL-6) dependency and
CD45 positivity. Moreover, we showed that IL-6 stimulation led to the
induction of expression of CD45 and cellular proliferation. Using
independent experimental approaches, we could show that the
IL-6-induced effects were closely linked to CD45 expression. First,
sorting out CD45+ and CD45 subsets of
U-266 cell line followed by IL-6 stimulation, only the
CD45+ cells showed a proliferative advantage after IL-6
stimulation. Second, IL-6 stimulation of sorted CD45
cells was gradually followed by phenotypic conversion to
CD45+ cells that started after 2 days as judged by the
detection of CD45 mRNA by reverse transcription polymerase chain
reaction (RT-PCR) and immunophenotypic analysis by flow
cytometry. Withdrawal of IL-6 from the medium led to gradual loss of
CD45 expression in CD45+ flow-sorted U-266 cells. Third,
the use of vanadate, a potent inhibitor of protein tyrosine phosphatase
(PTP), abrogated the IL-6-induced proliferation in the
CD45+ myeloma cells. On the other hand, cellular
proliferation induced by IL-6 was not affected by the serine-threonine
phosphatase inhibitor okadaic acid. Our data show that the expression
pattern of CD45 in myeloma cell lines is heterogeneous and show for the
first time that CD45 expression can be induced by IL-6 stimulation. Finally, these data shed some light on the biological role of CD45 in
myeloma by determining the proliferative population among myeloma
cells.
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