The effects of large extracellular vesicles from cancer cells adapted to acidosis or with ER stress on endothelial activation and permeability

• Grant number: 23/05006-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: February 01, 2024
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Vanessa Morais Freitas
• Grantee: Ana Sayuri Yamagata
• Supervisor: Edmond Young
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Toronto (U of T), Canada
• Associated to the scholarship: 20/15751-5 - Transmission of ER stress mediated by exosomes from tumor cells to endothelial cells: effects in autophagy, angiogenesis and endothelial activation, BP.DD

Abstract

Increase in endothelial activation and permeability are crucial steps in metastasis. In the tumor microenvironment, cancer cells typically suffer endoplasmic reticulum stress and extracellular acidosis. These conditions are associated with cancer progression and treatment resistance. Large extracellular vesicles (LEV) are important mediators in the communication between cancer cells and endothelial cells facilitating metastasis. The aim of this study is to investigate if LEV from breast cancer cells adapted to acidosis or that had previously suffered endoplasmic reticulum (ER) stress alter adhesion of cancer cells to the endothelium or alter endothelial permeability. Large extracellular vesicles (LEV) will be isolated from MDA-MB-231 human triple-negative breast cancer cells by centrifugation. LEV will be quantified by nanoparticle tracking analysis (NTA) and BCA assay. Adhesion of cancer cells and endothelial permeability will be assessed using a porous membrane-based microfluidic device. Additionally, extravasation of cancer cells through an endothelial monolayer forming a luminal tube in a microfluidic system will be assessed. (AU)