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Exp Cell Res. 2010 Jul 1;316(11):1816-28. doi: 10.1016/j.yexcr.2010.03.013. Epub 2010 Mar 20.

Bone marrow stromal cell interaction reduces syndecan-1 expression and induces kinomic changes in myeloma cells.

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  • 1Department of Gasteroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands. g.fuhler@erasmusmc.nl <g.fuhler@erasmusmc.nl>

Abstract

CD138 (Syndecan 1) is a heparan sulfate proteoglycan that concentrates heparan sulfate-binding growth factors on the surface of normal and malignant plasma cells (multiple myeloma, MMC). Recent studies have shown the presence of a CD138-negative fraction of MMC within myelomatous bone marrow (BM). We employed kinome array technology to characterize this fraction at a molecular level, using a myeloma cell line model. Compared to CD138-positive cells, CD138-negative MMC showed (i) a reduced activity of kinases involved in cell cycle progression, in agreement with a decreased labeling index and (ii) reduced Rho signaling to F-actin. Interestingly, CD138 mRNA and protein expression was reduced upon interaction of MM cells with stromal cell lines and primary mesenchymal cultures, which was accompanied by the acquisition of an increased Bcl6/Blimp1 ratio. Co-culture induced an increased activity of kinases involved in adhesion and a decreased S-phase transition in both CD138-positive and -negative fractions. In addition, CD138-negative MMC demonstrated an increased STAT3 and ERK1/2 activation compared to CD138+ MMC, in agreement with a lower sensitivity to compound exposure. The presence of a less mature, more resistant CD138-negative myeloma cell fraction within bone marrow microniches might contribute to high incidence of relapse of Myeloma patients.

PMID:
20307537
[PubMed - indexed for MEDLINE]
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