Role of metabolism in polarization of monocytes to pro-angiogenic / pro-tumorigenic tumor-associated macrophages

• Applicant: Dr. Christer Bäck
• Subject Area: Gastroenterology ; Immunology ; Cell Biology
• Term: from 2012 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 229103497

During organ and tumor development and remodeling, macrophages support angiogenesis, not only by secreting pro-angiogenic growth factors and matrix-remodeling proteases, but also by physically interacting with the sprouting endothelial cells (EC) to assist the formation of complex vascular networks. This vessel growth is interrelated to a differentiation from quiescent ECs to tip and stalk cells form a new vessel sprout. Unpublished data from the host institute (Vesalius Research Center; KU Leuven, Belgium) indicates that such a distinct differentiation requires a specific metabolic rewiring within the ECs. Current research indicates also that specific modes of immunity are linked at a molecular, cellular and organ level to such a switch in energy metabolism.This project therefore aims to characterize and manipulate the metabolic program of tumor-associated macrophages (TAMs), either for the pro-angiogenic / pro-tumorigenic “non-classic” M2-TAMs or the anti-angiogenic / tumor-suppressing “classic” M1-TAMs. On this base, I will investigate whether TAM-specific metabolic pathways can be targeted to find new approaches in anti-cancer therapy.Therefore, I will accomplish different in vitro and in vivo techniques that will allow me to evaluate (i) the activity of glucose and glutamin metabolism in M1- and M2-TAMs, (ii) the role of the different metabolisms in differentiation of TAMs in vitro and in vivo and (iii) the capability of compounds that inhibit these metabolic pathways for a potential therapeutical role in cancer treatment.

• DFG Programme: Research Fellowships
• International Connection: Belgium
• Host: Professor Dr. Peter Carmeliet, Ph.D.