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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4914-4923. Prepublished online as a Blood First Edition Paper on March 5, 2007; DOI 10.1182/blood-2006-08-043232. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-043232v1 109/11/4914    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mahtouk, K. Articles by Klein, B. Search for Related Content PubMed PubMed Citation Articles by Mahtouk, K. Articles by Klein, B. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma Karène Mahtouk1,2, Dirk Hose3, Pierre Raynaud1,2, Michael Hundemer3, Michel Jourdan2, Eric Jourdan5, Veronique Pantesco2, Marion Baudard5, John De Vos1,2,4, Marion Larroque2, Thomas Moehler3, Jean-Francois Rossi4,5, Thierry Rème1,2, Hartmut Goldschmidt3,6, and Bernard Klein1,2,4 1 Centre Hospitalier Universitaire (CHU) Montpellier, Institute of Research in Biotherapy, Montpellier, France; 2 Institut National de la Santé et de la Recherche Médicale (INSERM), U847, Montpellier, France; 3 Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Germany; 4 Université Montpellier1, France; 5 CHU Montpellier, Department of Hematology and Clinical Oncology, Montpellier, France; 6 Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany 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 HSPEpos 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Erratum for Seidel et al., Blood 95 (2) 388-392 Blood 2000 95: 2197. [Full Text] [PDF] This article has been cited by other articles: S. Bhattacharyya, K. Kotlo, S. Shukla, R. S. Danziger, and J. K. Tobacman Distinct Effects of N-Acetylgalactosamine-4-sulfatase and Galactose-6-sulfatase Expression on Chondroitin Sulfates J. Biol. Chem., April 11, 2008; 283(15): 9523 - 9530. [Abstract] [Full Text] [PDF] K. Mahtouk, D. Hose, J. De Vos, J. Moreaux, M. Jourdan, J. F. Rossi, T. Reme, H. Goldschmidt, and B. Klein Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic Applications Clin. Cancer Res., December 15, 2007; 13(24): 7289 - 7295. [Abstract] [Full Text] [PDF] Y. Yang, V. MacLeod, Y. Dai, Y. Khotskaya-Sample, Z. Shriver, G. Venkataraman, R. Sasisekharan, A. Naggi, G. Torri, B. Casu, et al. The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy Blood, September 15, 2007; 110(6): 2041 - 2048. [Abstract] [Full Text] [PDF]

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