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Science 1 December 1995:
Vol. 270. no. 5241, pp. 1500 - 1502
DOI: 10.1126/science.270.5241.1500
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Reports

Definition of Two Angiogenic Pathways by Distinct Integrins

Martin Friedlander,  Peter C. Brooks,  Robert W. Shaffer,  Christine M. Kincaid,  Judith A. Varner,  David A. Cheresh

Angiogenesis depends on cytokines and vascular cell adhesion events. Two cytokine-dependent pathways of angiogenesis were shown to exist and were defined by their dependency on distinct vascular cell integrins. In vivo angiogenesis in corneal or chorioallantoic membrane models induced by basic fibroblast growth factor or by tumor necrosis factor-alpha depended on alpha(v)beta(3), whereas angiogenesis initiated by vascular endothelial growth factor, transforming growth factor-alpha, or phorbol ester depended on alpha(v)beta(5). Antibody to each integrin selectively blocked one of these pathways, and a cyclic peptide antagonist of both integrins blocked angiogenesis stimulated by each cytokine tested. These pathways are further distinguished by their sensitivity to calphostin C, an inhibitor of protein kinase C that blocked angiogenesis potentiated by alpha(v)beta(5) but not by alpha(v)beta(3).


M. Friedlander, R. W. Shaffer, C. M. Kincaid, Robert Mealey Laboratory for the Study of Macular Degenerations, Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
P. C. Brooks and D. A. Cheresh, Departments of Immunology and Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
J. A. Varner, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.


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S. E. Woodman, A. W. Ashton, W. Schubert, H. Lee, T. M. Williams, F. A. Medina, J. B. Wyckoff, T. P. Combs, and M. P. Lisanti (2003)
Am. J. Pathol. 162, 2059-2068
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Synergistic Effect of TNF-{alpha} in Soluble VCAM-1-Induced Angiogenesis Through {alpha}4 Integrins.
S. Nakao, T. Kuwano, T. Ishibashi, M. Kuwano, and M. Ono (2003)
J. Immunol. 170, 5704-5711
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Thymidine Phosphorylase and 2-Deoxyribose Stimulate Human Endothelial Cell Migration by Specific Activation of the Integrins {alpha}5{beta}1 and {alpha}V{beta}3.
K. A. Hotchkiss, A. W. Ashton, and E. L. Schwartz (2003)
J. Biol. Chem. 278, 19272-19279
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{alpha}v{beta}3 Integrin Antagonist S247 Decreases Colon Cancer Metastasis and Angiogenesis and Improves Survival in Mice.
N. Reinmuth, W. Liu, S. A. Ahmad, F. Fan, O. Stoeltzing, A. A. Parikh, C. D. Bucana, G. E. Gallick, M. A. Nickols, W. F. Westlin, et al. (2003)
Cancer Res. 63, 2079-2087
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Cardiovascular ephrinB2 function is essential for embryonic angiogenesis.
S. S. Gerety and D. J. Anderson (2003)
Development 129, 1397-1410
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A Role for {alpha}v{beta}3 Integrin During Implantation in the Rabbit Model.
M. J. Illera, P.L. Lorenzo, Y.-t. Gui, S. A. Beyler, K.B.C. Apparao, and B. A. Lessey (2003)
Biol Reprod 68, 766-771
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Noninvasive Assessment of Angiogenesis by Ultrasound and Microbubbles Targeted to {alpha}v-Integrins.
H. Leong-Poi, J. Christiansen, A. L. Klibanov, S. Kaul, and J. R. Lindner (2003)
Circulation 107, 455-460
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Domain Swapping in a COOH-terminal Fragment of Platelet Factor 4 Generates Potent Angiogenesis Inhibitors.
M. Hagedorn, L. Zilberberg, J. Wilting, X. Canron, G. Carrabba, C. Giussani, M. Pluderi, L. Bello, and A. Bikfalvi (2002)
Cancer Res. 62, 6884-6890
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Prostaglandin E2 Promotes Integrin alpha Vbeta 3-dependent Endothelial Cell Adhesion, Rac-activation, and Spreading through cAMP/PKA-dependent Signaling.
O. Dormond, M. Bezzi, A. Mariotti, and C. Ruegg (2002)
J. Biol. Chem. 277, 45838-45846
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