Bone marrow stromal cell interaction reduces Syndecan-1 expression and induces kinomic changes in myeloma cells
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). W...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 March 2010
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| In: |
Experimental cell research
Year: 2010, Volume: 316, Issue: 11, Pages: 1816-1828 |
| ISSN: | 1090-2422 |
| DOI: | 10.1016/j.yexcr.2010.03.013 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.yexcr.2010.03.013 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0014482710001205 
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| Author Notes: | Gwenny M. Fuhler, Mirjam Baanstra, Daniel Chesik, Rajesh Somasundaram, Anja Seckinger, Dirk Hose, Maikel P. Peppelenbosch, Nico A. Bos |
| Summary: | 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. |
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| Item Description: | Gesehen am 18.07.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1090-2422 |
| DOI: | 10.1016/j.yexcr.2010.03.013 |