Snake Venom Disintegrins and Cell Migration 英文参考文献.docVIP

Toxins 2010, 2, 2606-2621; doi:10.3390/toxins2112606 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Snake Venom Disintegrins and Cell Migration Heloisa S. Selistre-de-Araujo *, Carmen L. S. Pontes, Cyntia F. Montenegro and Ana Carolina B. M. Martin Departamento de Ciências Fisiológicas, Universidade Federal de S?o Carlos, S?o Carlos, SP, 13565-905, Brazil; E-Mails: carmenpontes@.br (C.L.S.P.); cyntia_montenegro@ (C.F.M.); carol_gau@.br (A.C.B.M.M.) * Author to whom correspondence should be addressed; E-Mail: hsaraujo@ufscar.br; Tel.: +55-1633518333; Fax: +55-1633518401. Received: 24 August 2010; in revised form: 15 October 2010 / Accepted: 18 October 2010 / Published: 29 October 2010 Abstract: Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin-binding proteins such as the snake venom disintegrins that inhibit integrin- mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion. Keywords: cell migration; disintegrin; snake venom; ADAM; αvβ3 integrin 1. Introduction Metastasis is one the major causes of death in patients with cancer. In order for a tumor to grow and metastasize, both tumor and endothelial cells must migrate and invade surrounding tissues [1,2]. Endothe