Targeting EXT1 reveals a crucial role for heparan sulfate in the growth of multiple myeloma

Rogier M. Reijmers, Richard W. J. Groen, Henk Rozemuller, Annemieke Kuil, Anneke de Haan-Kramer, Tamás Csikós, Anton C. M. Martens, Marcel Spaargaren, Steven T. Pals

Research output: Contribution to journalArticleAcademicpeer-review

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Expression of the heparan sulfate proteoglycan syndecan-1 is a hallmark of both normal and multiple myeloma (MM) plasma cells. Syndecan-1 could affect plasma cell fate by strengthening integrinmediated adhesion via its core protein and/or by accommodating and presenting soluble factors via its HS side chains. Here, we show that inducible RNAi-mediated knockdown of syndecan-1 in human MM cells leads to reduced growth rates and a strong increase of apoptosis. Importantly, knockdown of EXT1, a copolymerase critical for HS chain biosynthesis, had similar effects. Using an innovative myeloma xenotransplantation model in Rag-2(-/-)gamma(-/-)(c) mice, we demonstrate that induction of EXT1 knockdown in vivo dramatically suppresses the growth of bone marrow localized myeloma. Our findings provide direct evidence that the HS chains of syndecan-1 are crucial for the growth and survival of MM cells within the bone marrow environment, and indicate the HS biosynthesis machinery as a potential treatment target in MM. (Blood. 2010; 115: 601-604)
Original languageEnglish
Pages (from-to)601-604
Number of pages4
Issue number3
Publication statusPublished - 21 Jan 2010


  • Animals
  • Antineoplastic Combined Chemotherapy Protocols/administration & dosage
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • DNA-Binding Proteins/genetics
  • Doxycycline/administration & dosage
  • Drug Delivery Systems
  • Gene Targeting
  • Heparitin Sulfate/metabolism
  • Humans
  • Immunoglobulin gamma-Chains/genetics
  • Mice
  • Mice, Knockout
  • Multiple Myeloma/drug therapy
  • N-Acetylglucosaminyltransferases/antagonists & inhibitors
  • RNA, Small Interfering/pharmacology
  • Syndecan-1/genetics
  • Xenograft Model Antitumor Assays

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