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Blood, 15 July 2008, Vol. 112, No. 2, pp. 374-382. Prepublished online as a Blood First Edition Paper on March 14, 2008; DOI 10.1182/blood-2007-10-120253. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-10-120253v1 112/2/374    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 Qiang, Y.-W. Articles by Yaccoby, S. Search for Related Content PubMed PubMed Citation Articles by Qiang, Y.-W. Articles by Yaccoby, S. Related Collections Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth Ya-Wei Qiang1, John D. Shaughnessy, Jr1, and Shmuel Yaccoby1 1 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock Canonical Wnt signaling is central to normal bone homeostasis, and secretion of Wnt signaling inhibitors by multiple myeloma (MM) cells contributes to MM-related bone resorption and disease progression. The aim of this study was to test the effect of Wnt3a on bone disease and growth of MM cells in vitro and in vivo. Although Wnt3a activated canonical signaling in the majority of MM cell lines and primary cells tested, Wnt3a had no effect on MM cell growth in vitro. Moreover, forced expression of Wnt3a in H929 MM cells conferred no growth advantage over empty vector-transfected cells in vitro or importantly when grown subcutaneously in severe combined immunodeficient (SCID) mice. Importantly, although H929 cells stably expressing an empty vector injected into human bone grew rapidly and induced a marked reduction in bone mineral density, bones engrafted with Wnt3a-expressing H929 cells were preserved, exhibited increased osteoblast-to-osteoclast ratios, and reduced tumor burden. Likewise, treatment of myelomatous SCID-hu mice, carrying primary disease, with recombinant Wnt3a stimulated bone formation and attenuated MM growth. These results provide further support of the potential anabolic and anti-MM effects of enhancing Wnt signaling in the bone. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Wnt signaling: bone's defense against myeloma Claire M. Edwards Blood 2008 112: 216-217. [Full Text] [PDF] This article has been cited by other articles: J. Dutta-Simmons, Y. Zhang, G. Gorgun, M. Gatt, M. Mani, T. Hideshima, K. Takada, N. E. Carlson, D. E. Carrasco, Y.-T. Tai, et al. Aurora kinase A is a target of Wnt/{beta}-catenin involved in multiple myeloma disease progression Blood, September 24, 2009; 114(13): 2699 - 2708. [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] M. Fulciniti, P. Tassone, T. Hideshima, S. Vallet, P. Nanjappa, S. A. Ettenberg, Z. Shen, N. Patel, Y.-t. Tai, D. Chauhan, et al. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma Blood, July 9, 2009; 114(2): 371 - 379. [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] J. J. Pinzone, B. M. Hall, N. K. Thudi, M. Vonau, Y.-W. Qiang, T. J. Rosol, and J. D. Shaughnessy Jr The role of Dickkopf-1 in bone development, homeostasis, and disease Blood, January 15, 2009; 113(3): 517 - 525. [Abstract] [Full Text] [PDF] R. Modarresi, Z. Xiang, M. Yin, and J. Laurence WNT/{beta}-Catenin Signaling Is Involved in Regulation of Osteoclast Differentiation by Human Immunodeficiency Virus Protease Inhibitor Ritonavir: Relationship to Human Immunodeficiency Virus-Linked Bone Mineral Loss Am. J. Pathol., January 1, 2009; 174(1): 123 - 135. [Abstract] [Full Text] [PDF] B. Chen, H. Wu, Y. Zeng, J. E Freeman III, D. Herman, J. D. Shaughnessy Jr., B. Barlogie, and J. Epstein Myeloma and Osteolytic Bone Disease: Is DKK1 All It Takes?. Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 1695 - 1695. [Abstract] 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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