Alternagin-C, an agonist of a2b1 integrin, inhibits tumor cell adhesion and cell migration.

¹Terruggi, C.H.B., ²Crépin, M. and ¹Selistre-de-Araujo, H.S.

1 Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, SP, 13565-905, Brazil; 2 Laboratoire d’Hémostase, Endothelium et Angiogénèse (Unité INSERM 553), Hôpital Saint Louis, 75010 Paris, France.

Alternagin-C (Alt-C), a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, interacts with the major collagen I receptor, the a2b1 integrin, inhibiting collagen binding. In the present study, we investigated the effects of Alt-C on tumor cell adhesion and cell migration in vitro. Alt-C inhibited the adhesion of ECV-304, HeLa and MDA-MB-231 cells to collagen I (IC50 of 1.66, 1.38 and 0.95mM respectively).  Alt-C does not inhibit the binding and the migration of MCF-7 cell line to collagen type I, probably due the other collagen receptors in this cell type. In addition, when immobilized on plate wells, Alt-C supports the adhesion of these cell lines. Alt-C does not detach cells that were previously bound to collagen I. Alt-C in the presence of collagen I stimulates the migration of MDA-MB-231 cell but in greater concentrations it inhibits cell migration.  These findings provide that the biologic activities of Alt-C can be used as an angiogenic therapy.

Support: FAPESP (processo- 00/09495-2), CNPq-INSERM.