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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2041-2048. Prepublished online as a Blood First Edition Paper on May 29, 2007; DOI 10.1182/blood-2007-04-082495. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-04-082495v1 110/6/2041    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yang, Y. Articles by Sanderson, R. D. Search for Related Content PubMed PubMed Citation Articles by Yang, Y. Articles by Sanderson, R. D. Related Collections Neoplasia Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy Yang Yang1, Veronica MacLeod2, Yuemeng Dai2, Yekaterina Khotskaya-Sample1, Zachary Shriver3, Ganesh Venkataraman3, Ram Sasisekharan4, Annamaria Naggi5, Giangiacomo Torri5, Benito Casu5, Israel Vlodavsky6, Larry J. Suva7, Joshua Epstein8, Shmuel Yaccoby8, John D. Shaughnessy, Jr8, Bart Barlogie8, and Ralph D. Sanderson1,8 1 Department of Pathology, University of Alabama at Birmingham; 2 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock; 3 Momenta Pharmaceuticals, Cambridge, MA; 4 Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge; 5 G. Ronzoni Institute for Chemical and Biochemical Research, Milan, Italy; 6 Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel; 7 Center for Orthopedic Research, Department of Orthopedic Surgery, University of Arkansas for Medical Sciences, Little Rock; 8 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock The heparan sulfate proteoglycan syndecan-1 is expressed by myeloma cells and shed into the myeloma microenvironment. High levels of shed syndecan-1 in myeloma patient sera correlate with poor prognosis and studies in animal models indicate that shed syndecan-1 is a potent stimulator of myeloma tumor growth and metastasis. Overexpression of extracellular endosulfatases, enzymes which remove 6-O sulfate groups from heparan sulfate chains, diminishes myeloma tumor growth in vivo. Together, these findings identify syndecan-1 as a potential target for myeloma therapy. Here, 3 different strategies were tested in animal models of myeloma with the following results: (1) treatment with bacterial heparinase III, an enzyme that degrades heparan sulfate chains, dramatically inhibited the growth of primary tumors in the human severe combined immunodeficient (SCID-hu) model of myeloma; (2) treatment with an inhibitor of human heparanase, an enzyme that synergizes with syndecan-1 in promoting myeloma progression, blocked the growth of myeloma in vivo; and (3) knockdown of syndecan-1 expression by RNAi diminished and delayed myeloma tumor development in vivo. These results confirm the importance of syndecan-1 in myeloma pathobiology and provide strong evidence that disruption of the normal function or amount of syndecan-1 or its heparan sulfate chains is a valid therapeutic approach for this cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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