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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1980-1988. Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-06-094680. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-06-094680v1 111/4/1980    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 Zhang, Z. Articles by Zutter, M. M Search for Related Content PubMed PubMed Citation Articles by Zhang, Z. Articles by Zutter, M. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 14, 2007 Accepted November 16, 2007 21 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor-cell specific manner Zhonghua Zhang, Norma E. Ramirez, Thomas E. Yankeelov, Zhengzhi Li, Laura E. Ford, Ying Qi, Ambra Pozzi, and Mary M Zutter* Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN, United States Departments of Radiology & Radiological Sciences, Biomedical Engineering, Physics & Astronomy, and Institute of Imaging Science, Vanderbilt University School of Medicine, Nashville, TN, United States Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, United States * Corresponding author; email: mary.zutter{at}vanderbilt.edu. To define the role of the 21 integrin in pathologic angiogenesis, we investigated tumor-associated growth and angiogenesis in wild-type and 2-null mice. Our findings reveal that the 21 integrin plays an important role in angiogenesis via regulation of VEGFR1 expression. When challenged with B16F10 melanoma cells, mice lacking 21 integrin expression exhibit increased tumor angiogenesis associated with upregulated VEGFR1 expression. In contrast, there was no 21 integrin-dependent difference in the angiogenic response to Lewis lung carcinoma (LLC) cells. Interestingly, whereas B16F10 cells secrete high levels of PLGF, LLC cells produce high levels of VEGF, but low levels of PLGF. The 21 integrin-dependent difference in angiogenesis was restored to LLC cells by expression of PLGF, strongly suggesting that the angiogenic phenotype and tumor growth in the 2-null host is dependent on specific interactions between the tumor cell and the genetically-defined integrin repertoire of the host microenvironment. Thus, integrin alpha2-null mice represent an example of genetic alterations of "the soil" determining response to the "seed". CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. C. Roman, J. M. Carvajal-Gonzalez, E. M. Rico-Leo, and P. M. Fernandez-Salguero Dioxin Receptor Deficiency Impairs Angiogenesis by a Mechanism Involving VEGF-A Depletion in the Endothelium and Transforming Growth Factor-{beta} Overexpression in the Stroma J. Biol. Chem., September 11, 2009; 284(37): 25135 - 25148. [Abstract] [Full Text] [PDF] T. D. Abair, N. Bulus, C. Borza, M. Sundaramoorthy, R. Zent, and A. Pozzi Functional analysis of the cytoplasmic domain of the integrin {alpha}1 subunit in endothelial cells Blood, October 15, 2008; 112(8): 3242 - 3254. [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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