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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1524-1532. Prepublished online as a Blood First Edition Paper on October 5, 2006; DOI 10.1182/blood-2006-08-041970. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-08-041970v1 109/4/1524    most recent 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 Takeda, Y. Articles by Hemler, M. E. Search for Related Content PubMed PubMed Citation Articles by Takeda, Y. Articles by Hemler, M. E. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro Yoshito Takeda1, Alexander R. Kazarov1, Catherine E. Butterfield2, Benjamin D. Hopkins3, Laura E. Benjamin3, Arja Kaipainen2, and Martin E. Hemler1 1 Dana-Farber Cancer Institute, Boston, MA; 2 Vascular Biology Program, Children's Hospital, Boston, MA; 3 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA Tetraspanin protein CD151 is abundant on endothelial cells. To determine whether CD151 affects angiogenesis, Cd151-null mice were prepared. Cd151-null mice showed no vascular defects during normal development or during neonatal oxygen-induced retinopathy. However, Cd151-null mice showed impaired pathologic angiogenesis in other in vivo assays (Matrigel plug, corneal micropocket, tumor implantation) and in the ex vivo aortic ring assay. Cd151-null mouse lung endothelial cells (MLECs) showed normal adhesion and proliferation, but marked alterations in vitro, in assays relevant to angiogenesis (migration, spreading, invasion, Matrigel contraction, tube and cable formation, spheroid sprouting). Consistent with these functional impairments, and with the close, preferential association of CD151 with laminin-binding integrins, Cd151-null MLECs also showed selective signaling defects, particularly on laminin substrate. Adhesion-dependent activation of PKB/c-Akt, e-NOS, Rac, and Cdc42 was diminished, but Raf, ERK, p38 MAP kinase, FAK, and Src were unaltered. In Cd151-null MLECs, connections were disrupted between laminin-binding integrins and at least 5 other proteins. In conclusion, CD151 modulates molecular organization of laminin-binding integrins, thereby supporting secondary (ie, after cell adhesion) functions of endothelial cells, which are needed for some types of pathologic angiogenesis in vivo. Selective effects of CD151 on pathologic angiogenesis make it a potentially useful target for anticancer therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. L. Johnson, N. Winterwood, K. A. DeMali, and C. S. Stipp Tetraspanin CD151 regulates RhoA activation and the dynamic stability of carcinoma cell-cell contacts J. Cell Sci., July 1, 2009; 122(13): 2263 - 2273. [Abstract] [Full Text] [PDF] F. Zhang, J. Kotha, L. K. Jennings, and X. A. Zhang Tetraspanins and vascular functions Cardiovasc Res, July 1, 2009; 83(1): 7 - 15. [Abstract] [Full Text] [PDF] R. Sadej, H. Romanska, G. Baldwin, K. Gkirtzimanaki, V. Novitskaya, A. D. Filer, Z. Krcova, R. Kusinska, J. Ehrmann, C. D. Buckley, et al. CD151 Regulates Tumorigenesis by Modulating the Communication between Tumor Cells and Endothelium Mol. Cancer Res., June 1, 2009; 7(6): 787 - 798. [Abstract] [Full Text] [PDF] C.-W. Chien, S.-C. Lin, Y.-Y. Lai, B.-W. Lin, S.-C. Lin, J.-C. Lee, and S.-J. Tsai Regulation of CD151 by Hypoxia Controls Cell Adhesion and Metastasis in Colorectal Cancer Clin. Cancer Res., December 15, 2008; 14(24): 8043 - 8051. [Abstract] [Full Text] [PDF] O. Barreiro, M. Zamai, M. Yanez-Mo, E. Tejera, P. Lopez-Romero, P. N. Monk, E. Gratton, V. R. Caiolfa, and F. Sanchez-Madrid Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms J. Cell Biol., November 3, 2008; 183(3): 527 - 542. [Abstract] [Full Text] [PDF] M. Yanez-Mo, O. Barreiro, P. Gonzalo, A. Batista, D. Megias, L. Genis, N. Sachs, M. Sala-Valdes, M. A. Alonso, M. C. Montoya, et al. MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells Blood, October 15, 2008; 112(8): 3217 - 3226. [Abstract] [Full Text] [PDF] Y. Takeda, P. He, I. Tachibana, B. Zhou, K. Miyado, H. Kaneko, M. Suzuki, S. Minami, T. Iwasaki, S. Goya, et al. Double Deficiency of Tetraspanins CD9 and CD81 Alters Cell Motility and Protease Production of Macrophages and Causes Chronic Obstructive Pulmonary Disease-like Phenotype in Mice J. Biol. Chem., September 19, 2008; 283(38): 26089 - 26097. [Abstract] [Full Text] [PDF] X. H. Yang, A. L. Richardson, M. I. Torres-Arzayus, P. Zhou, C. Sharma, A. R. Kazarov, M. M. Andzelm, J. L. Strominger, M. Brown, and M. E. Hemler CD151 Accelerates Breast Cancer by Regulating {alpha}6 Integrin Function, Signaling, and Molecular Organization Cancer Res., May 1, 2008; 68(9): 3204 - 3213. [Abstract] [Full Text] [PDF] T. Lekishvili, E. Fromm, M. Mujoomdar, and F. 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