| Bone marrow stromal cell interaction reduces syndecan-1 expression and induces kinomic changes in myeloma cells. | |
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MedLine Citation:
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PMID: 20307537 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Gwenny M Fuhler; Mirjam Baanstra; Daniel Chesik; Rajesh Somasundaram; Anja Seckinger; Dirk Hose; Maikel P Peppelenbosch; Nico A Bos |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-20 |
Journal Detail:
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Title: Experimental cell research Volume: 316 ISSN: 1090-2422 ISO Abbreviation: Exp. Cell Res. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-05-31 Completed Date: 2010-06-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
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Languages: eng Pagination: 1816-28 Citation Subset: IM |
Affiliation:
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Department of Gasteroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands. g.fuhler@erasmusmc.nl <g.fuhler@erasmusmc.nl> |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Bone Marrow Cells
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pathology*,
physiology* Cell Cycle Cell Differentiation Cell Line Cell Line, Tumor Coculture Techniques Drug Resistance, Neoplasm Humans Multiple Myeloma / drug therapy, genetics, pathology*, physiopathology* Neoplastic Stem Cells / pathology, physiology Phosphotransferases / metabolism RNA, Messenger / genetics, metabolism RNA, Neoplasm / genetics, metabolism Recurrence Signal Transduction Stromal Cells / pathology, physiology Syndecan-1 / genetics, metabolism* Transcription Factors / metabolism rho GTP-Binding Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/RNA, Neoplasm; 0/SDC1 protein, human; 0/Syndecan-1; 0/Transcription Factors; EC 2.7.-/Phosphotransferases; EC 3.6.5.2/rho GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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