Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action 英文参考文献.docVIP

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Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action 英文参考文献.doc

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Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action 英文参考文献

Pharmaceuticals 2010, 3, 1241-1278; doi:10.3390/ph3041241 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action Marco Rusnati 1,*, Chiara Urbinati 1, Silvia Bonifacio 2, Marco Presta 1 and Giulia Taraboletti 2 1 Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, 25123, Italy; E-Mails: urbinati@med.unibs.it (C.U.); presta@med.unibs.it (M.P.) 2 Tumor Angiogenesis Unit, Department of Oncology, Mario Negri Institute for Pharmacological Research, Bergamo, Italy; E-Mails: bonifacio@marionegri.it (S.B.); taraboletti@marionegri.it (G.T.) * Author to whom correspondence should be addressed. E-Mail: rusnati@med.unibs.it; Tel.: +39-030-3717315; Fax: +39-030-3701157. Received: 14 February 2010; in revised form: 20 April 2010 / Accepted: 22 April 2010 / Published: 23 April 2010 Abstract: Uncontrolled neovascularization occurs in several angiogenesis-dependent diseases, including cancer. Neovascularization is tightly controlled by the balance between angiogenic growth factors and antiangiogenic agents. The various natural angiogenesis inhibitors identified so far affect neovascularization by different mechanisms of action. Thrombospondin-1 (TSP-1) is a matricellular modular glycoprotein that acts as a powerful endogenous inhibitor of angiogenesis. It acts both indirectly, by sequestering angiogenic growth factors and effectors in the extracellular environment, and directly, by inducing an antiangiogenic program in endothelial cells following engagement of specific receptors including CD36, CD47, integrins and proteoglycans (all involved in angiogenesis ). In view of its central, multifaceted role in angiogenesis, TSP-1 has served as a source of antiangiogenic tools, including TSP-