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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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Main Authors: Mahtouk, Karène (Author) , Hose, Dirk (Author) , Raynaud, Pierre (Author) , Hundemer, Michael (Author) , Jourdan, Michel (Author) , Jourdan, Eric (Author) , Pantesco, Veronique (Author) , Baudard, Marion (Author) , De Vos, John (Author) , Larroque, Marion (Author) , Möhler, Thomas (Author) , Rossi, Jean-Francois (Author) , Rème, Thierry (Author) , Goldschmidt, Hartmut (Author) , Klein, Bernard (Author)
Format: Article (Journal)
Language:English
Published: [1 June 2007]
In: Blood
Year: 2007, Volume: 109, Issue: 11, Pages: 4914-4923
ISSN:1528-0020
DOI:10.1182/blood-2006-08-043232
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2006-08-043232
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Author Notes: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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Summary: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.
Item Description:Gesehen am 11.02.2022
Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2006-08-043232

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