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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1168-1177. Prepublished online as a Blood First Edition Paper on April 10, 2007; DOI 10.1182/blood-2007-01-066282. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-066282v1 110/4/1168    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 Boosani, C. S. Articles by Sudhakar, A. Search for Related Content PubMed PubMed Citation Articles by Boosani, C. S. Articles by Sudhakar, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 5, 2007 Accepted April 7, 2007 Regulation of COX-2 mediated signaling by 3 type IV non-collagenous domain in tumor angiogenesis Chandra Shekhar Boosani, Arjuna P Mannam, Dominic Cosgrove, Rita Silva, Kairbaan M Hodivala-Dilke, Venkateshwar G Keshamouni, and Akulapalli Sudhakar* Department of Genetics, Cell Signaling and Angiogenesis Laboratory, Boys Town National Research Hospital, Omaha, NE, United States Department of Neurology, University of Connecticut School of Medicine, Hartford Hospital, Hartford, CT, United States Department of Genetics, Gene Expression Laboratory, Boys Town National Research Hospital, Omaha, NE, United States Richard Dimbleby Department of Cancer Research, Cancer Research UK, Cell Adhesion and Disease Laboratory, St. Thomas Hospital, London, United Kingdom Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, United States Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, United States * Corresponding author; email: akulapallis{at}boystown.org. Human 3 chain, non-collagenous domain of type IV collagen (3(IV)NC1) inhibits angiogenesis and tumor growth. These biological functions are attributed, in part, to the binding of 3(IV)NC1 to V3 and 31 integrins. 3(IV)NC1 binds to V3 integrin, leading to translation inhibition by inhibiting focal adhesion kinase/phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 pathways. In the present study we evaluated the role of 31 and V3 integrins in tube formation and regulation of cyclooxygenase-2 (COX-2) upon 3(IV)NC1 stimulation. We found that while both integrins were required for the inhibition of tube formation by 3(IV)NC1 in endothelial cells whereas, only 31 integrin was sufficient to regulate COX-2 in hypoxic endothelial cells. We show that binding of 3(IV)NC1 to 31 integrin leads to inhibition of COX-2-mediated pro-angiogenic factors, VEGF and bFGF, by regulating IB/NFB axis and is independent of V3 integrin. Furthermore, 3 integrin null endothelial cells when treated with 3(IV)NC1 inhibited hypoxia-mediated COX-2 expression, where as COX-2 inhibition was not observed in 3 integrin null endothelial cells indicating that, regulation of COX-2 by 3(IV)NC1 is mediated by integrinn31. Taken together, our in vitro and in vivo findings demonstrate that 31 integrin is critical for 3(IV)NC1-mediated inhibition of COX-2 dependent angiogenic signaling and inhibition of tumor progression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. S. Boosani, N. Nalabothula, V. Munugalavadla, D. Cosgrove, V. G. Keshamoun, N. Sheibani, and A. Sudhakar FAK and p38-MAP Kinase-Dependent Activation of Apoptosis and Caspase-3 in Retinal Endothelial Cells by {alpha}1(IV)NC1 Invest. Ophthalmol. Vis. Sci., October 1, 2009; 50(10): 4567 - 4575. [Abstract] [Full Text] [PDF] R. Silva, G. D'Amico, K. M. Hodivala-Dilke, and L. E. Reynolds Integrins: The Keys to Unlocking Angiogenesis Arterioscler Thromb Vasc Biol, October 1, 2008; 28(10): 1703 - 1713. [Abstract] [Full Text] [PDF]

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