Transmission of ER stress mediated by exosomes from tumor cells to endothelial cells: effects in autophagy, angiogenesis and endothelial activation

Abstract

Breast Cancer is the second Cancer type that most affects women. Of these patients, metastasis is one of the main causes of death. The angiogenesis, the entrance and exit of tumor cells from the circulation are fundamental steps in metastasis. Our group observed that incubation of tumor cells in acid pH increased the expression of genes involved in angiogenesis. Acid pH and other adverse conditions in the tumor microenvironment cause Endoplasmic Reticulum (ER) stress. ER stress, signaled by the Unfolded Protein Response (UPR), favors angiogenesis in the tumor. Studies have shown the existence of a phenomenon termed in the literature as "transmission of ER stress", in which cells release factors in the medium after undergoing ER stress, and such factors activate the UPR in recipient cells. ER stress increases the release of Extracellular Vesicles (EVs), important mediators of intercellular communication, and these vesicles could possibly mediate this transmission. EVs released from tumor cells can induce autophagy in other cells, which can stimulate angiogenesis in endothelial cells. In this project, we intent do investigate whether extracellular vesicles, released by tumor cells in response to ER stress induced by acid pH or protein unfolding, modulate angiogenesis, the expression of adhesion molecules and the permeability of endothelial cells. (AU)