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
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-
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