Exploring novel anti-cancer strategies by targeting endothelial metabolism: an unexplored pathway.

Like tumor cells, endothelial cells (ECs) exhibit aerobic glycolysis, referring to their preference to the anaerobic breakdown of glucose despite the ample availability of oxygen, for the production of energy. It remains outstanding whether this metabolic reprogramming is required to allow them to invade and vascularize the hypoxic tumor. In addition, the role of the EC mitochondria as the metabolic powerhouse is unclear. This project therefore aims at characterizing and manipulating the metabolic program of ECs, either during migration/proliferation or vessel stabilization, with emphasis on the role of the mitochondria herein. Moreover, I will explore whether EC-specific metabolic pathways can be targeted to increase the efficiency of overall anticancer therapy. To accomplish these goals, I will apply different in vitro and in vivo techniques that will allow me to evaluate 1) expression of metabolic genes in migrating/proliferating versus stabilized ECs; 2) the structure and function of the mitochondria in EC; 3) EC properties and their capacity to induce vessel sprouting after altering mitochondrial function using specific inhibitors of lipid synthesis and mitochondrial respiration. Ultimately, I will use these inhibitors in well established developmental and pathological angiogenic models to evaluate their possible therapeutical role in cancer treatment.

Keywords:Metabolism, Endothelium, Angiogenesis, Tumor

Disciplines:Morphological sciences, Oncology, Physiology, Cardiac and vascular medicine