The role of PFKFB3 in angiogenesis: a model to study breast cancer

• Grant number: 13/17512-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2014
• End date: January 31, 2015
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Manoel João Batista Castello Girão
• Grantee: Giovana Aparecida Gonçalves
• Supervisor: Peter Carmeliet
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Leuven, Leuven (KU Leuven), Belgium

Abstract

Breast cancer (BC) is the most frequently diagnosed cancer in women, affecting one in eight women. Despite improved treatment strategies, this disease has become the focus of numerous scientific papers in order to introduce new techniques, drugs and more effective treatments. Endothelial cells (ECs) line blood vessels to supply oxygen and nutrients to tissues. Abnormal blood vessel growth (angiogenesis) promotes cancer growth and spread. Current strategies to inhibit angiogenesis rely on the inhibition of the growth factor VEGF. However, the efficacy of this treatment strategy is limited by intrinsic refractoriness and resistance. Since ECs need increased amounts of energy when proliferating and migrating, blocking their energy supply and depriving their "engine" from nutrients is an attractive yet unexplored strategy to inhibit angiogenesis. Recently, the host laboratory (Laboratory of Angiogenesis & Neurovascular link, Vesalius Research Center, VRC) discovered that PFKFB3, a key regulator of the glycolytic breakdown of glucose to produce energy, regulates angiogenesis in vitro by controlling EC migration and proliferation (De Bock et al., Cell, 201319). Using a multidisciplinary approach, combining molecular and cellular biology with conditional mouse genetics, I propose to investigate the role and functional relevance of PFKFB3 in angiogenesis in health and disease, and explore the therapeutic potential of PFKFB3 blockade as novel anti-angiogenic strategy for cancer treatment. The results promise to provide unprecedented insights that will be useful for the development of a novel anti-glycolytic anti-angiogenesis therapy for tumor angiogenesis and growth. (AU)