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Study of the role of insularin as antagonist of tumoral and endothelial cell adhesion to platelets

Grant number: 11/21535-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2012
Effective date (End): July 31, 2012
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Maisa Splendore Della Casa
Grantee:Rafaela Silva Mendonça
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The tumor cell adhesion is an important step in the progression of tumor metastasis and has the important participation of platelets. Mechanisms that drive tumors involve the capture of the adhesive interactions of tumor cells with endothelial cells and platelets. Clinical statistics show that half of the patients with cancer have platelet activation and thrombosis. Recently, intensive studies have been conducted using the network of integrin-targeted control of adhesion and migration of tumor cells. A family of integrins, overexpressed in tumor cells, have been recognized as regulators of various neoplastic processes because of the ability to facilitate adhesion and migration of cancer cells. The literature showed the importance of Disintegrins, proteins isolated from Viperidae snake venoms, as important tools for the development of antagonists of cell adhesion-dependent pathologies such as thrombosis and angiogenesis. The Disintegrins inhibit platelet aggregation and cell adhesion, with structural and functional heterogeneity. The RGD-Disintegrins have an affinity for integrin aIIbb3, a5b1, and avb3. Data recently published by our group demonstrated that insular in a GST-INS, a recombinant Disintegrins ARGDNP from Bothrops insularis venom, was able to inhibit platelet aggregation via the ADP and the inhibit endothelial cell adhesion to fibrinogen. These data encouraged us through this project, to elucidate the inhibition of tumor and endothelial cell adhesion to platelets by GST-INS, thereby contributing to the elucidation and insertion of this molecule in the development of agents and tumor anti-angiogenic.(AU)

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