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Role of Insularin on inibition of platelet agregation induced by SK-Mel-28 cells: in vitro studies

Grant number: 14/21546-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2015
Effective date (End): December 31, 2015
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Maisa Splendore Della Casa
Grantee:Lilian Gomes de Oliveira
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Tumor cell adhesion is an important step in the progression of tumor metastasis and has a significant participation of platelets. Capture mechanisms that drive tumor involve tumor cell adhesive interactions with endothelial cells and platelets. Clinical statistics show that half of patients with cancer, shows platelet activation and thrombosis. Recently, intensive studies have shown that integrins as an important network in control of tumor cells adhesion and migration.The family of integrins overexpressed in tumor cells, have been recognized as regulators of various neoplastic processes due to the ability to facilitate the adhesion and migration of cancer cells. The literature elucidating the importance of disintegrins, proteins isolated from snake venom Viperidae as important tools for the development of antagonists of cell adhesion -dependent diseases such as thrombosis and angiogenesis. The disintegrins inhibit platelet aggregation and cell adhesion, presenting structural and functional heterogeneity. The RGD-disintegrins have affinity for alphaIIbbeta3, alpha5beta1 and alphavbeta3 integrins. Data recently published by our group demonstrated that insularin, GST - INS, a recombinant ARGDNP disintegrin from Bothropsinsularis, was able to inhibit platelet aggregation via ADP and inhibit endothelial cell adhesion to fibrinogen significantly. These data encouraged us through this project, to study the role of GST- INS on inhibition of adhesion of melanoma cells with platelets and on inhibition of platelet aggregation induced by these cells. Thus, these studies can contribute to the elucidate the role of this molecule in the development of anti-tumor agents.