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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3271-3278. Prepublished online as a Blood First Edition Paper on December 22, 2005; DOI 10.1182/blood-2005-09-3830. This Article Full Text (PDF) All Versions of this Article: 2005-09-3830v1 107/8/3271    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 Karadag, A. Articles by Croucher, P. I Search for Related Content PubMed PubMed Citation Articles by Karadag, A. Articles by Croucher, P. I Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 23, 2005 Accepted October 25, 2005 ADAM-9 (mdc-9/meltrin-), a member of the a disintegrin and metalloproteinase family, regulates myeloma cell induced interleukin-6 production in osteoblasts by direct interaction with the v5-integrin Abdullah Karadag, Min Zhou, and Peter I Croucher* Division of Clinical Sciences, University of Sheffield Medical School, Sheffield, United Kingdom; Craniofacial & Skeletal Diseases Branch, National Institue of Dental and Craniofacial Research, National Institutes of Health,, Bethesda, MD, USA; Department of Biochemistry, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey Craniofacial & Skeletal Diseases Branch, National Institue of Dental and Craniofacial Research, National Institutes of Health,, Bethesda, MD, USA Division of Clinical Sciences, University of Sheffield Medical School, Sheffield, United Kingdom * Corresponding author; email: p.croucher{at}sheffield.ac.uk. ADAM-9, a member of the A Disintegrin And Metalloproteinase family, contains both metalloproteinase and disintegrin domains. Myeloma cell lines express ADAM-9; however, its function and role in the pathophysiology of multiple myeloma is unknown. The aim of this study was to establish whether primary myeloma cells express ADAM-9, whether ADAM-9 regulates IL-6 production in osteoblasts (hOBs) and whether ADAM-9 interacts with specific integrin heterodimers, and the identity of downstream signaling pathways. Primary myeloma cells demonstrated increased expression of ADAM-9 (p<0.01). ADAM-9 promoted a 5-fold increase in IL-6, but not IL1 mRNA, and a dose- and time-dependent increase in IL-6 production by hOBs (p<0.01). IL-6 induction was inhibited by an antibody to the v5-integrin (p<0.01), but not by antibodies to other integrin heterodimers. ADAM-9 was shown to bind directly to the v5-integrin on hOB. Antibodies to ADAM-9 and v5-integrin inhibited myeloma cell-induced IL-6 production by hOBs (p<0.01). Furthermore, inhibitors of p38 MAPK and cPLA2, but not NF-kB and JAK2, signaling pathways inhibited ADAM-9-induced IL-6 production by hOBs (p<0.01). These data demonstrate that ADAM-9, expressed by myeloma cells stimulates IL-6 production in hOBs by binding the v5-integrin. This may have important consequences for the growth and survival of myeloma cells in bone. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. L.R. Brito, B. Walker, M. Jenner, N. J. Dickens, N. J.M. Brown, F. M. Ross, A. Avramidou, J. A.E. Irving, D. Gonzalez, F. E. Davies, et al. MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells Haematologica, January 1, 2009; 94(1): 78 - 86. [Abstract] [Full Text] [PDF] C. M. Findley, M. J. Cudmore, A. Ahmed, and C. D. Kontos VEGF Induces Tie2 Shedding via a Phosphoinositide 3-Kinase/Akt Dependent Pathway to Modulate Tie2 Signaling Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2619 - 2626. [Abstract] [Full Text] [PDF]

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