Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma
The heparan sulfate (HS) proteoglycan, syndecan-1, plays a major role in multiple myeloma (MM) by concentrating heparin-binding growth factors on the surface of MM cells (MMCs). Using Affymetrix microarrays and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we show that the gene...
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| Hauptverfasser: | , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
[1 June 2007]
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| In: |
Blood
Year: 2007, Jahrgang: 109, Heft: 11, Pages: 4914-4923 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2006-08-043232 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2006-08-043232
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| Verfasserangaben: | Karène Mahtouk, Dirk Hose, Pierre Raynaud, Michael Hundemer, Michel Jourdan, Eric Jourdan, Veronique Pantesco, Marion Baudard, John De Vos, Marion Larroque, Thomas Moehler, Jean-Francois Rossi, Thierry Rème, Hartmut Goldschmidt, Bernard Klein |
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| 245 | 1 | 0 | |a Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma |c Karène Mahtouk, Dirk Hose, Pierre Raynaud, Michael Hundemer, Michel Jourdan, Eric Jourdan, Veronique Pantesco, Marion Baudard, John De Vos, Marion Larroque, Thomas Moehler, Jean-Francois Rossi, Thierry Rème, Hartmut Goldschmidt, Bernard Klein |
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| 520 | |a The heparan sulfate (HS) proteoglycan, syndecan-1, plays a major role in multiple myeloma (MM) by concentrating heparin-binding growth factors on the surface of MM cells (MMCs). Using Affymetrix microarrays and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we show that the gene encoding heparanase (HPSE), an enzyme that cleaves HS chains, is expressed by 11 of 19 myeloma cell lines (HMCLs). In HSPE(pos) HMCLs, syndecan-1 gene expression and production of soluble syndecan-1, unlike expression of membrane syndecan-1, were significantly increased. Knockdown of HPSE by siRNA resulted in a decrease of syndecan-1 gene expression and soluble syndecan-1 production without affecting membrane syndecan-1 expression. Thus, HPSE influences expression and shedding of syndecan-1. Contrary to HMCLs, HPSE is expressed in only 4 of 39 primary MMC samples, whereas it is expressed in 36 of 39 bone marrow (BM) microenvironment samples. In the latter, HPSE is expressed at a median level in polymorphonuclear cells and T cells; it is highly expressed in monocytes and osteoclasts. Affymetrix data were validated at the protein level, both on HMCLs and patient samples. We report for the first time that a gene's expression mainly in the BM environment (ie, HSPE) is associated with a shorter event-free survival of patients with newly diagnosed myeloma treated with high-dose chemotherapy and stem cell transplantation. Our study suggests that clinical inhibitors of HPSE could be beneficial for patients with MM. | ||
| 650 | 4 | |a Aged | |
| 650 | 4 | |a Bone Marrow | |
| 650 | 4 | |a Bone Marrow Cells | |
| 650 | 4 | |a Cell Line, Tumor | |
| 650 | 4 | |a Gene Expression Regulation, Enzymologic | |
| 650 | 4 | |a Gene Expression Regulation, Neoplastic | |
| 650 | 4 | |a Glucuronidase | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Middle Aged | |
| 650 | 4 | |a Monocytes | |
| 650 | 4 | |a Multiple Myeloma | |
| 650 | 4 | |a Neutrophils | |
| 650 | 4 | |a Osteoclasts | |
| 650 | 4 | |a Prognosis | |
| 650 | 4 | |a Syndecan-1 | |
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| 773 | 0 | 8 | |i Enthalten in |t Blood |d Washington, DC : American Society of Hematology, 1946 |g 109(2007), 11, Seite 4914-4923 |h Online-Ressource |w (DE-627)266886647 |w (DE-600)1468538-3 |w (DE-576)075961938 |x 1528-0020 |7 nnas |a Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma |
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