The role of integrins on exosome binding to the extracellular matrix and its contribution to tumor progression

Abstract

Cancer is a serious human health problem worldwide. Metastasis is responsible for as much as 90% of cancer-associated mortality, and remains as the most poorly understood component of cancer pathogenesis. Tumor cells are capable to proliferate and create a microenviroment, as well as migrate to distant sites by a cross talk with the surrounding environment. In the last years, evidence is accumulating that this tumor cell-host cross talk, which includes long distance communication, mostly relies on tumor exosomes (TEX). TEX are ~40 - ~100 nm vesicles derived from luminal membranes of multivesicular bodies secreted to exterior, carrying bioactive cargoes that promote cell migration and tumor progression. Recently studies demonstrated that they also contribute to directional persistence and speed of cells migrating in vivo, through associated extracellular matrix (ECM) molecules that appear to be targeted to exosomes by integrin receptors. We have developed a post-doctoral project with promising preliminary results in this issue (FAPESP 2014/18747-8). To improve this work, the present project proposes a scientific collaboration between the Laboratório de Bioquímica e Biologia Molecular (LBBM) from Universidade Federal de São Carlos (UFSCar) and the Weaver Laboratory at Vanderbilt University. Research will focus on the role of exosomes on tumor cell communication with the microenviroment and with the ECM in special. In addition, the importance of integrins in these interactions will be explored through multiple methods, including employing an RGD-based integrin inhibitor. These studies will contribute to the post doctor scientific background on exosomes research and state of the art of methodologies in cell communication. It is also important to highlight that this project is part of a thematic project from FAPESP (2013/00798-2).