Estudo do papel da integrina αvβ3 de vesículas extracelulares de células tumorais de mama sobre células endoteliais em modelo de co-cultura

Abstract

Breast cancer is one of the most worrisome diseases because of its high rate of morbidity and mortality. It can be caused by different types of tumors, most of which are treated with hormone therapy. However, triple negative breast cancer is an exception to such treatment because it lacks receptors for hormones such as estrogen and progesterone, making it one of the most aggressive tumors and without specific therapy. The high mortality rate is correlated with metastasis, a process in which tumor cells acquire an invasive migratory phenotype, dissociate from the primary tumor, and invade adjacent tissues or a site distant from the primary site. Tumor cells secrete extracellular vesicles (EVs) capable of altering the microenvironment in which they are found, making it suitable for the establishment of a new tumor. These vesicles interact with other cells through integrins present on their surface. Integrins are heterodimeric adhesion receptors and fundamental in the context of EV uptake. In this way, EVs reprogram healthy stromal cells to act in tumor function, secreting extracellular matrix remodeling factors. In the present proposal, we aimed to verify the role of αvβ3 integrin in the transfer of EVs from triple-negative breast tumor cells (MDA MB-231-GFP-CD63) to endothelial cells (HUVEC) and the subsequent phenotypic transformation. We used the disintegrin DisBa-01 as a blocking tool for αvβ3 integrin, since previous works by the group showed the importance of this receptor in the uptake and adhesion of EVs. The differential of this work lies in the experimental strategy, using the Quasi-vivo system of cell co-culture, which allows intercellular communication through the continuous flow of the culture medium. For the analysis of Evs exchange and cell phenotype, morphological fluorescence assays were used.