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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2833-2842. Prepublished online as a Blood First Edition Paper on December 19, 2007; DOI 10.1182/blood-2007-03-077685. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-077685v1 111/5/2833    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 Edwards, C. M. Articles by Mundy, G. R. Search for Related Content PubMed PubMed Citation Articles by Edwards, C. M. Articles by Mundy, G. R. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo Claire M. Edwards1,2, James R. Edwards2,3, Seint T. Lwin3, Javier Esparza2, Babatunde O. Oyajobi2, Brandon McCluskey2, Steven Munoz3, Barry Grubbs2, and Gregory R. Mundy2,3 1 Vanderbilt Center for Bone Biology, Department of Cancer Biology, Vanderbilt University, Nashville, TN; 2 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio; and 3 Vanderbilt Center for Bone Biology, Department of Medicine/Clinical Pharmacology, Vanderbilt University, Nashville, TN There is increasing evidence to suggest that the Wnt signaling pathway plays a critical role in the pathogenesis of myeloma bone disease. In the present study, we determined whether increasing Wnt signaling within the bone marrow microenvironment in myeloma counteracts development of osteolytic bone disease. C57BL/KaLwRij mice were inoculated intravenously with murine 5TGM1 myeloma cells, resulting in tumor growth in bone and development of myeloma bone disease. Lithium chloride (LiCl) treatment activated Wnt signaling in osteoblasts, inhibited myeloma bone disease, and decreased tumor burden in bone, but increased tumor growth when 5TGM1 cells were inoculated subcutaneously. Abrogation of β-catenin activity and disruption of Wnt signaling in 5TGM1 cells by stable overexpression of a dominant-negative TCF4 prevented the LiCl-induced increase in subcutaneous growth but had no effect on LiCl-induced reduction in tumor burden within bone or on osteolysis in myeloma-bearing mice. Together, these data highlight the importance of the local microenvironment in the effect of Wnt signaling on the development of myeloma bone disease and demonstrate that, despite a direct effect to increase tumor growth at extraosseous sites, increasing Wnt signaling in the bone marrow microenvironment can prevent the development of myeloma bone disease and inhibit myeloma growth within bone in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. M. Edwards Wnt signaling: bone's defense against myeloma Blood, July 15, 2008; 112(2): 216 - 217. [Full Text] [PDF] X. Li, A. Pennisi, and S. Yaccoby Role of decorin in the antimyeloma effects of osteoblasts Blood, July 1, 2008; 112(1): 159 - 168. [Abstract] [Full Text] [PDF]

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