Pharmaceuticals 2010, 3(4), 1241-1278; doi:10.3390/ph3041241
Review

Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action

1 Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, 25123, Italy 2 Tumor Angiogenesis Unit, Department of Oncology, Mario Negri Institute for Pharmacological Research, Bergamo, Italy
* Author to whom correspondence should be addressed.
Received: 14 February 2010; in revised form: 20 April 2010 / Accepted: 22 April 2010 / Published: 23 April 2010
(This article belongs to the Special Issue Angiogenesis Inhibitors)
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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-1 fragments, synthetic peptides and peptidomimetics, gene therapy strategies, and agents that up-regulate TSP-1 expression. This review discusses TSP-1-based inhibitors of angiogenesis, their mechanisms of action and therapeutic potential, drawing our experience with angiogenic growth factor-interacting TSP-1 peptides, and the possibility of exploiting them to design novel antiangiogenic agents.
Keywords: angiogenesis; tumor; integrins; interactions; thrombospondin-1

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MDPI and ACS Style

Rusnati, M.; Urbinati, C.; Bonifacio, S.; Presta, M.; Taraboletti, G. Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action. Pharmaceuticals 2010, 3, 1241-1278.

AMA Style

Rusnati M, Urbinati C, Bonifacio S, Presta M, Taraboletti G. Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action. Pharmaceuticals. 2010; 3(4):1241-1278.

Chicago/Turabian Style

Rusnati, Marco; Urbinati, Chiara; Bonifacio, Silvia; Presta, Marco; Taraboletti, Giulia. 2010. "Thrombospondin-1 as a Paradigm for the Development of Antiangiogenic Agents Endowed with Multiple Mechanisms of Action." Pharmaceuticals 3, no. 4: 1241-1278.

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