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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2149-2154. Prepublished online as a Blood First Edition Paper on May 11, 2004; DOI 10.1182/blood-2004-01-0236. This Article Full Text (PDF) All Versions of this Article: 2004-01-0236v1 104/7/2149    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 Mori, Y. Articles by Yoneda, T. Search for Related Content PubMed PubMed Citation Articles by Mori, Y. Articles by Yoneda, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 20, 2004 Accepted April 16, 2004 Anti-4 Integrin Antibody Suppresses the Development of Multiple Myeloma and Associated Osteoclastic Osteolysis Yoshihisa Mori*, Nobuaki Shimizu, Mark Dallas, Maryla Niewolna, Beryl Story, Paul J Williams, Gregory R Mundy, and Toshiyuki Yoneda Division of Endocrinology, Department of Medicine, The University of Texas Health Science Center, San Antonio, TX, USA * Corresponding author; email: moriy-tky{at}umin.ac.jp. Supporting roles of stromal cells in preferential colonization of myeloma cells in bone marrow and development of associated osteoclastic osteolysis through cell-cell interactions have been indicated. Here we examined the effects of a monoclonal antibody to 4 integrin (anti-4 Ab) that disrupts myeloma cell-stromal cell interactions mediated via 41 integrin and VCAM-1 on myeloma cell growth in bone marrow and accompanying osteolysis. The 5TGM1 murine myeloma cells stably transfected with the firefly luciferase (5TGM1/luc) were inoculated from tail vein in bg/xid/nd mice. The anti-4 Ab decreased VCAM-1-stimulated 5TGM1/luc cell growth in culture. Preventative administration of the anti-4 Ab suppressed the elevation of serum IgG2b levels, decreased 5TGM1/luc tumor burden with increased apoptosis in bone and spleen, reduced bone destruction with diminished number of osteoclasts and prolonged survival of 5TGM1/luc-bearing mice. In contrast, therapeutic administration of the antibody failed to show these effects. However, therapeutic administration of the antibody combined with melphalan significantly suppressed serum IgG2b levels and tumor burden in bone. Our results suggest that the interactions with stromal cells via 41/VCAM-1 are critical to the development of myeloma and associated osteolysis and that disruption of these interactions using anti-4 Ab is a potential therapeutic approach for myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Burger, P. Ghia, A. Rosenwald, and F. Caligaris-Cappio The microenvironment in mature B-cell malignancies: a target for new treatment strategies Blood, October 15, 2009; 114(16): 3367 - 3375. [Abstract] [Full Text] [PDF] F. Silvestris, P. Cafforio, M. De Matteo, N. Calvani, M. A. Frassanito, and F. Dammacco Negative Regulation of the Osteoblast Function in Multiple Myeloma through the Repressor Gene E4BP4 Activated by Malignant Plasma Cells Clin. Cancer Res., October 1, 2008; 14(19): 6081 - 6091. [Abstract] [Full Text] [PDF] M. B. Meads, L. A. Hazlehurst, and W. S. Dalton The Bone Marrow Microenvironment as a Tumor Sanctuary and Contributor to Drug Resistance Clin. Cancer Res., May 1, 2008; 14(9): 2519 - 2526. [Abstract] [Full Text] [PDF] S. T. Pals, D. J. J. de Gorter, and M. Spaargaren Lymphoma dissemination: the other face of lymphocyte homing Blood, November 1, 2007; 110(9): 3102 - 3111. [Abstract] [Full Text] [PDF] M. Kobune, H. Chiba, J. Kato, K. Kato, K. Nakamura, Y. Kawano, K. Takada, R. Takimoto, T. Takayama, H. Hamada, et al. Wnt3/RhoA/ROCK signaling pathway is involved in adhesion-mediated drug resistance of multiple myeloma in an autocrine mechanism Mol. Cancer Ther., June 1, 2007; 6(6): 1774 - 1784. [Abstract] [Full Text] [PDF] N. Giuliani, V. Rizzoli, and G. D. Roodman Multiple myeloma bone disease: pathophysiology of osteoblast inhibition Blood, December 15, 2006; 108(13): 3992 - 3996. [Abstract] [Full Text] [PDF] N. Giuliani, S. Colla, F. Morandi, M. Lazzaretti, R. Sala, S. Bonomini, M. Grano, S. Colucci, M. Svaldi, and V. Rizzoli Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation Blood, October 1, 2005; 106(7): 2472 - 2483. [Abstract] [Full Text] [PDF] D. L. Olson, L. C. Burkly, D. R. Leone, B. M. Dolinski, and R. R. Lobb Anti-{alpha}4 integrin monoclonal antibody inhibits multiple myeloma growth in a murine model Mol. Cancer Ther., January 1, 2005; 4(1): 91 - 99. [Abstract] [Full Text] [PDF]

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