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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-12-3905. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3905v1 102/1/311    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 Oyajobi, B. O. Articles by Mundy, G. R. Search for Related Content PubMed PubMed Citation Articles by Oyajobi, B. O. Articles by Mundy, G. R. Related Collections Chemokines, Cytokines, and Interleukins Neoplasia Phagocytes Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 311-319 NEOPLASIA Dual effects of macrophage inflammatory protein-1 on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease Babatunde O. Oyajobi, Giovanni Franchin, Paul J. Williams, Donna Pulkrabek, Anjana Gupta, Steve Munoz, Barry Grubbs, Ming Zhao, Di Chen, Barbara Sherry, and Gregory R. Mundy From the Departments of Molecular Medicine and Medicine, University of Texas Health Science Center at San Antonio (UTHSCSA), TX; Molecular Therapeutics Division, CTRC (Cancer Therapy and Research Center) Institute for Drug Development, San Antonio, TX; and Laboratory of Cytokine Biology, The Picower Institute for Medical Research, Manhasset, NY. Recent data have implicated macrophage inflammatory protein-1 (MIP-1) in multiple myeloma (MM)-associated osteolysis. However, it is unclear whether the chemokine's effects are direct, to enhance osteolysis, or indirect and mediated through a reduction in tumor burden, or both. It is also unclear whether MIP-1 requires other factors such as receptor activator of nuclear factor-B ligand (RANKL) for its effects on bone. In murine 5TGM1 (Radl) myeloma-bearing mice, administration of neutralizing anti-MIP-1 antibodies reduced tumor load assessed by monoclonal paraprotein titers, prevented splenomegaly, limited development of osteolytic lesions, and concomitantly reduced tumor growth in bone. To determine the effects of MIP-1 on bone in vivo, Chinese hamster ovary (CHO) cells secreting human MIP-1 (CHO/MIP-1) were inoculated into athymic mice. Mice bearing intramuscular CHO/MIP-1 tumors developed lytic lesions at distant skeletal sites, which occurred earlier and were larger than those in mice with CHO/empty vector (EV) tumors. When experimental metastases were induced via intracardiac inoculation, mice bearing CHO/MIP-1 tumors developed hypercalcemia and significantly more osteolytic lesions than mice bearing CHO/EV tumors, with intramedullary CHO/MIP-1 tumors associated with significantly more tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts. Injection of recombinant MIP-1 over calvariae of normal mice evoked a striking increase in osteoclast formation, an effect dependent on RANK/RANKL signaling because MIP-1 had no effect in RANK-/- mice. Together, these results establish that MIP-1 is sufficient to induce MM-like destructive lesions in bone in vivo. Because, in the 5TGM1 model, blockade of osteoclastic resorption in other situations does not decrease tumor burden, we conclude that MIP-1 exerts a dual effect in myeloma, on osteoclasts, and tumor cells. (Blood. 2003;102:311-319) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: New insight into myeloma lytic bone disease Joshua Epstein Blood 2003 102: 5. [Full Text] [PDF] This article has been cited by other articles: C. M. Edwards, J. R. Edwards, S. T. Lwin, J. Esparza, B. O. Oyajobi, B. McCluskey, S. Munoz, B. Grubbs, and G. R. Mundy Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo Blood, March 1, 2008; 111(5): 2833 - 2842. [Abstract] [Full Text] [PDF] S. T. Shu, M. V.P. Nadella, W. P. Dirksen, S. A. Fernandez, N. K. Thudi, J. L. Werbeck, M. D. Lairmore, and T. J. 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