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 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 language | English |
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Pages (from-to) | 601-604 |
Number of pages | 4 |
Journal | Blood |
Volume | 115 |
Issue number | 3 |
DOIs | |
Publication status | Published - 21 Jan 2010 |
Keywords
- 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