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

Abstract

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 integrin-mediated 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.

Original languageEnglish
Pages (from-to)601-4
Number of pages4
JournalBlood
Volume115
Issue number3
DOIs
Publication statusPublished - 21 Jan 2010

Cite this

Reijmers, R. M., Groen, R. W. J., Rozemuller, H., Kuil, A., de Haan-Kramer, A., Csikós, T., ... Pals, S. T. (2010). Targeting EXT1 reveals a crucial role for heparan sulfate in the growth of multiple myeloma. Blood, 115(3), 601-4. https://doi.org/10.1182/blood-2009-02-204396