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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 1, 2007 Accepted November 14, 2007 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 Edwards*, James R Edwards, Seint T Lwin, Javier Esparza, Babatunde O. Oyajobi, Brandon McCluskey, Steven Munoz, Barry Grubbs, and Gregory R. Mundy Department of Cancer Biology, Vanderbilt Center for Bone Biology, Vanderbilt University, Nashville, TN, United States Department of Medicine/Clinical Pharmacology, Vanderbilt Center for Bone Biology, Vanderbilt University, Nashville, TN, United States Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States * Corresponding author; email: claire.edwards{at}vanderbilt.edu. 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 -catenin activity and disruption of Wnt signaling in 5TGM1 cells by stable over-expression 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 extra-osseous 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: J. A. Fowler, G. R. Mundy, S. T. Lwin, C. C. Lynch, and C. M. Edwards A murine model of myeloma that allows genetic manipulation of the host microenvironment Dis. Model. Mech., November 1, 2009; 2(11-12): 604 - 611. [Abstract] [Full Text] [PDF] A. Pennisi, W. Ling, X. Li, S. Khan, J. D. Shaughnessy Jr, B. Barlogie, and S. Yaccoby The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth Blood, August 27, 2009; 114(9): 1803 - 1812. [Abstract] [Full Text] [PDF] Y.-W. Qiang, B. Hu, Y. Chen, Y. Zhong, B. Shi, B. Barlogie, and J. D. Shaughnessy Jr Bortezomib induces osteoblast differentiation via Wnt-independent activation of {beta}-catenin/TCF signaling Blood, April 30, 2009; 113(18): 4319 - 4330. [Abstract] [Full Text] [PDF] E. Ashihara, E. Kawata, Y. Nakagawa, C. Shimazaski, J. Kuroda, K. Taniguchi, H. Uchiyama, R. Tanaka, A. Yokota, M. Takeuchi, et al. {beta}-Catenin Small Interfering RNA Successfully Suppressed Progression of Multiple Myeloma in a Mouse Model Clin. Cancer Res., April 15, 2009; 15(8): 2731 - 2738. [Abstract] [Full Text] [PDF] M. S. Raab, I. Breitkreutz, G. Tonon, J. Zhang, P. J. Hayden, T. Nguyen, J. H. Fruehauf, B. K. Lin, D. Chauhan, T. Hideshima, et al. 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