Evaluation of Ambiyomin-X effect in activation of endothelial cells by tumor microenvironment

• Grant number: 14/24512-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2015
• End date: June 30, 2016
• Field of knowledge: Biological Sciences - Biochemistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Ana Marisa Chudzinski-Tavassi
• Grantee: Mariana Costa Braga Schmidt
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Amblyomin-X (Amblyomma Factor Xa inhibitor) is a Kunitz-type protease inhibitor that inhibits FXa in presence of phospholipids or inhibits FX activation by extrinsic tenase complex (FT/FVIIa). This recombinant protein presents similarity with TFPI-1, a major regulator of coagulation process that also has an antitumor activity, as it has been described in literature. In a similar way, Amblyomin-X also presents antitumor effects and it is selective for tumor cells, probably due to its interaction with phosphatidylserine (PS) which is exposed on these cell surfaces. Interestingly, PS is also exposed in tumor vascular endothelium, which could be a uptake route of this molecule. Furthermore, Amblyomin-X is efficient in inhibition of angiogenesis by independent mechanisms of Vein Endothelial Growth Factor (VEGF) and inhibits human endothelial cells capacity to form tubes without compromising cell viability or morphologic alterations. Thereby, this antiangiogenic effect of Amblyomin-X could be associated with pericellular proteolysis and extracellular matrix remodeling, thereafter, it is associated with inhibition of cell migration needed to form tubes on endothelial cells. Thus, this project was elaborated in order to verify if Amblyomin-X is internalized by endothelial cells and if the induction of PS exposure or its blockade interferes in its uptake by this cell type. Besides, this project intend to analyze Amblyomin-X interference in oxidative conditions, on fibrinolytic proteins and extracellular matrix metalloproteinases production and cell migration, which will help in understanding the recombinant protein activity. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SCHMIDT, MARIANA COSTA BRAGA; MORAIS, KATIA L. P.; DE ALMEIDA, MAIRA ESTANISLAU SOARES; IQBAL, ASIF; GOLDFEDER, MAURICIO BARBUGIANI; CHUDZINSKI-TAVASSI, ANA MARISA. Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells. CELL ADHESION & MIGRATION, v. 14, n. 1, p. 129-138, JAN 1 2020. (13/07467-1, 15/50040-4, 14/24512-3)