SEARCH:   Advanced

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 Neoplasia Phagocytes Chemokines, Cytokines, and Interleukins 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: 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] O. Sezer Myeloma Bone Disease: Recent Advances in Biology, Diagnosis, and Treatment Oncologist, March 1, 2009; 14(3): 276 - 283. [Abstract] [Full Text] [PDF] N. Giuliani, G. Lisignoli, S. Colla, M. Lazzaretti, P. Storti, C. Mancini, S. Bonomini, C. Manferdini, K. Codeluppi, A. Facchini, et al. CC-Chemokine Ligand 20/Macrophage Inflammatory Protein-3{alpha} and CC-Chemokine Receptor 6 Are Overexpressed in Myeloma Microenvironment Related to Osteolytic Bone Lesions Cancer Res., August 15, 2008; 68(16): 6840 - 6850. [Abstract] [Full Text] [PDF] 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. Rosol A Novel Bioluminescent Mouse Model and Effective Therapy for Adult T-Cell Leukemia/Lymphoma Cancer Res., December 15, 2007; 67(24): 11859 - 11866. [Abstract] [Full Text] [PDF] S. Vallet, N. Raje, K. Ishitsuka, T. Hideshima, K. Podar, S. Chhetri, S. Pozzi, I. Breitkreutz, T. Kiziltepe, H. Yasui, et al. MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts Blood, November 15, 2007; 110(10): 3744 - 3752. [Abstract] [Full Text] [PDF] E. Terpos, O. Sezer, P. Croucher, and M.-A. Dimopoulos Myeloma bone disease and proteasome inhibition therapies Blood, August 15, 2007; 110(4): 1098 - 1104. [Abstract] [Full Text] [PDF] R. E. Miller, D. Branstetter, A. Armstrong, B. Kennedy, J. Jones, L. Cowan, J. Bussiere, and W. C. Dougall Receptor Activator of NF-{kappa}B Ligand Inhibition Suppresses Bone Resorption and Hypercalcemia but Does Not Affect Host Immune Responses to Influenza Infection J. Immunol., July 1, 2007; 179(1): 266 - 274. [Abstract] [Full Text] [PDF] B. O. Oyajobi, S. Munoz, R. Kakonen, P. J. Williams, A. Gupta, C. L. Wideman, B. Story, B. Grubbs, A. Armstrong, W. C. Dougall, et al. Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging Mol. Cancer Ther., June 1, 2007; 6(6): 1701 - 1708. [Abstract] [Full Text] [PDF] G. D. Roodman New potential targets for treating myeloma bone disease. Clin. Cancer Res., October 15, 2006; 12(20): 6270s - 6273s. [Abstract] [Full Text] [PDF] H. S. Yeh and J. R. Berenson Treatment for myeloma bone disease. Clin. Cancer Res., October 15, 2006; 12(20): 6279s - 6284s. [Abstract] [Full Text] [PDF] M. Yang, G. Mailhot, C. A. MacKay, A. Mason-Savas, J. Aubin, and P. R. Odgren Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1{gamma}) in osteoclastogenesis in vivo and in vitro Blood, March 15, 2006; 107(6): 2262 - 2270. [Abstract] [Full Text] [PDF] T. Matsumoto and M. Abe Myeloma-Bone Interaction: A Vicious Cycle IBMS BoneKEy, March 1, 2006; 3(3): 8 - 14. [Abstract] [Full Text] [PDF] T. Oshima, M. Abe, J. Asano, T. Hara, K. Kitazoe, E. Sekimoto, Y. Tanaka, H. Shibata, T. Hashimoto, S. Ozaki, et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2 Blood, November 1, 2005; 106(9): 3160 - 3165. [Abstract] [Full Text] [PDF] J. Turkson, S. Zhang, L. B. Mora, A. Burns, S. Sebti, and R. Jove A Novel Platinum Compound Inhibits Constitutive Stat3 Signaling and Induces Cell Cycle Arrest and Apoptosis of Malignant Cells J. Biol. Chem., September 23, 2005; 280(38): 32979 - 32988. [Abstract] [Full Text] [PDF] E. Terpos and M.-A. Dimopoulos Myeloma bone disease: pathophysiology and management Ann. Onc., August 1, 2005; 16(8): 1223 - 1231. [Abstract] [Full Text] [PDF] B. O. Oyajobi, C. M. Shipman, and G. R. Mundy Recent Insights into Myeloma Bone Disease IBMS BoneKEy, May 1, 2005; 2(5): 17 - 25. [Full Text] [PDF] L. Yin Chondroitin Synthase 1 Is a Key Molecule in Myeloma Cell-Osteoclast Interactions J. Biol. Chem., April 22, 2005; 280(16): 15666 - 15672. [Abstract] [Full Text] [PDF] M. Abe, K. Hiura, J. Wilde, A. Shioyasono, K. Moriyama, T. Hashimoto, S. Kido, T. Oshima, H. Shibata, S. Ozaki, et al. Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion Blood, October 15, 2004; 104(8): 2484 - 2491. [Abstract] [Full Text] [PDF] G. D. Roodman Mechanisms of Bone Metastasis N. Engl. J. Med., April 15, 2004; 350(16): 1655 - 1664. [Full Text] [PDF] J. W. Lee, H. Y. Chung, L. A. Ehrlich, D. F. Jelinek, N. S. Callander, G. D. Roodman, and S. J. Choi IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells Blood, March 15, 2004; 103(6): 2308 - 2315. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020