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This Article Full Text Full Text (PDF) 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 Michigami, T. Articles by Yoneda, T. Search for Related Content PubMed PubMed Citation Articles by Michigami, T. Articles by Yoneda, T. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2000, Vol. 96, No. 5, pp. 1953-1960 NEOPLASIA Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and 41-integrin enhances production of osteoclast-stimulating activity Toshimi Michigami, Nobuaki Shimizu, Paul J. Williams, Maria Niewolna, Sarah L. Dallas, Gregory R. Mundy, and Toshiyuki Yoneda From the Division of Endocrinology and Metabolism, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX; Department of Biochemistry, Osaka University Faculty of Dentistry, Suita, Osaka, Japan Myeloma is a unique hematologic malignancy that exclusively homes in the bone marrow and induces massive osteoclastic bone destruction presumably by producing cytokines that promote the differentiation of the hematopoietic progenitors to osteoclasts (osteoclastogenesis). It is recognized that neighboring bone marrow stromal cells influence the expression of the malignant phenotype in myeloma cells. This study examined the role of the interactions between myeloma cells and neighboring stromal cells in the production of osteoclastogenic factors to elucidate the mechanism underlying extensive osteoclastic bone destruction. A murine myeloma cell line 5TGM1, which causes severe osteolysis, expresses 41-integrin and tightly adheres to the mouse marrow stromal cell line ST2, which expresses the vascular cell adhesion molecule-1 (VCAM-1), a ligand for 41-integrin. Co-cultures of 5TGM1 with primary bone marrow cells generated tartrate-resistant acid phosphatase-positive multinucleated bone-resorbing osteoclasts. Co-cultures of 5TGM1 with ST2 showed increased production of bone-resorbing activity and neutralizing antibodies against VCAM-1 or 41-integrin inhibited this. The 5TGM1 cells contacting recombinant VCAM-1 produced increased osteoclastogenic and bone-resorbing activity. The activity was not blocked by the neutralizing antibody to known osteoclastogenic cytokines including interleukin (IL)-1, IL-6, tumor necrosis factor, or parathyroid hormone-related peptide. These data suggest that myeloma cells are responsible for producing osteoclastogenic activity and that establishment of direct contact with marrow stromal cells via 41-integrin/VCAM-1 increases the production of this activity by myeloma cells. They also suggest that the presence of stromal cells may provide a microenvironment that allows exclusive colonization of myeloma cells in the bone marrow. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Huston, X. Leleu, X. Jia, A.-S. Moreau, H. T. Ngo, J. Runnels, J. Anderson, Y. Alsayed, A. Roccaro, S. Vallet, et al. Targeting Akt and Heat Shock Protein 90 Produces Synergistic Multiple Myeloma Cell Cytotoxicity in the Bone Marrow Microenvironment Clin. Cancer Res., February 1, 2008; 14(3): 865 - 874. [Abstract] [Full Text] [PDF] L. H. Wang, X. Y. Yang, X. Zhang, and W. L. 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