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KMID : 0366220080430030127
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Korean Journal of Hematology
2008 Volume.43 No. 3 p.127 ~ p.137
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Stromal Cell-Derived Factor-1 Promotes Myeloma Cell Growth in Both Autocrine and Paracrine Manners
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Kim Seong-Woo
Lee Hyo-Jin
Kim Ha-Yon
Yun Hwan-Jung
Kim Sam-Yong
Jo Deog-Yeon
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Abstract
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Background: The question as to whether stromal cell-derived factor-1 (SDF-1) stimulated myeloma cell
growth has been controversial. We explored the possibility that SDF-1 may function as an autocrine
growth factor of myeloma cells.
Methods: CD138+ primary bone marrow myeloma cells and myeloma cell lines (RPMI8226, U266, and
ARH77) were used. Chemotaxis in response to SDF-1 of the cells was analyzed using TranswellsTM.
Cell proliferation was measured by a colorimetric assay. SDF-1 mRNA expression was analyzed by
RT-PCR (reverse-transcription-polymerase chain reaction). SDF-1 and interleukin-6 (IL-6) receptor expression
as well as signaling molecule phosphorylation levels, were examined using Western blot analysis.
Concentrations of SDF-1 in the cell culture supernatants were measured by ELISA assay.
Results: SDF-1 alone had no discernible effect on the proliferation of CD138+ primary myeloma cells
or myeloma cell lines. In contrast, SDF-1 significantly enhanced IL-6-induced proliferation of these cells.
SDF-1 up-regulated the expression of IL-6 receptor and enhanced phosphorylation of AKT in an additive
manner with IL-6. Co-culture of the myeloma cells with umbilical vein endothelial cells over-expressing
the SDF-1 gene revealed that SDF-1 played an important role in not only the migration of the cells
underneath the stromal cells but also the proliferation of the cells in contact with stromal cells. All the
myeloma cell lines expressed SDF-1 mRNA, and SDF-1 was detected in the culture supernatants of the
cells. The G protein-coupled receptor inhibitor, pertussis toxin, inhibited the proliferation of these cells
in suspension cultures.
Conclusion: SDF-1, most likely in concert with IL-6, enhanced the proliferation of myeloma cells in
a both paracrine and autocrine manner.
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KEYWORD
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Multiple myeloma, SDF-1, CXCR4, Interleukin-6, Bone marrow stromal cells
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