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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4294-4302. Prepublished online as a Blood First Edition Paper on August 23, 2005; DOI 10.1182/blood-2005-04-1730. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-04-1730v1 106/13/4294    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 Gao, L. Articles by Weilbaecher, K. Search for Related Content PubMed PubMed Citation Articles by Gao, L. Articles by Weilbaecher, K. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metastases prevented by osteoclast inhibition Ling Gao, Hongju Deng, Haibo Zhao, Angela Hirbe, John Harding, Lee Ratner, and Katherine Weilbaecher From the Department of Medicine, Division of Oncology, Washington University School of Medicine, St Louis; the Department of Cellular Biology and Physiology, Division of Oncology, Washington University School of Medicine, St Louis; and the Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO. One in 20 carriers of human T-cell leukemia virus type 1 (HTLV-1) will develop adult T-cell leukemia/lymphoma (ATL), a disease frequently associated with hypercalcemia, bone destruction, and a fatal course refractory to current therapies. Overexpression of the HTLV-1–encoded Tax oncoprotein under the human granzyme B promoter causes large granular lymphocytic leukemia/lymphomas in mice. We found that Tax+ mice spontaneously developed hypercalcemia, high-frequency osteolytic bone metastases, and enhanced osteoclast activity. We evaluated Tax tumors for the production of osteoclast-activating factors. Purification of Tax+ tumor cells and nonmalignant tumor-infiltrating lymphocytes demonstrated that each of these populations expressed transcripts for distinct osteoclast-activating factors. We then evaluated the effect of osteoclast inhibition on tumor formation. Mice doubly transgenic for Tax and the osteoclast inhibitory factor, osteoprotegerin, were protected from osteolytic bone disease and developed fewer soft-tissue tumors. Likewise, osteoclast inhibition with bone-targeted zoledronic acid protected Tax+ mice from bone and soft-tissue tumors and prolonged survival. Tax+ mice represent the first animal model of high-penetrance spontaneous osteolytic bone metastasis and underscore the critical role of nonmalignant host cells recruited by tumor cells in the process of cancer progression and metastasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. J. Wadas, H. Deng, J. E. Sprague, A. Zheleznyak, K. N. Weilbaecher, and C. J. Anderson Targeting the {alpha}v{beta}3 Integrin for Small-Animal PET/CT of Osteolytic Bone Metastases J. Nucl. Med., November 1, 2009; 50(11): 1873 - 1880. [Abstract] [Full Text] [PDF] P. D. Ottewell, J. K. Woodward, D. V. Lefley, C. A. Evans, R. E. Coleman, and I. Holen Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone Mol. Cancer Ther., October 1, 2009; 8(10): 2821 - 2832. [Abstract] [Full Text] [PDF] Z. Xu, M. A. Hurchla, H. Deng, O. Uluckan, F. Bu, A. Berdy, M. C. Eagleton, E. A. Heller, D. H. 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