Metabolic Flux Analysis in endothelial cells: a novel approach to define metabolic changes

Tumor development and growth is largely regulated by the formation of a network of blood vessels providing malignant cells nutrients and oxygen. This allows the tumor to grow and eventually triggers metastasis, in which cancer cells migrate to other organs. Blocking blood vessel formation is an important strategy in cancer treatment. So far, researchers have mainly focused on blocking the genetic signals produced by tumor cells, which trigger blood vessel formation (angiogenesis). Although initially successful, it is now clear that cancer cells, despite the availability of specific blockers, can override these therapies and hence rescue angiogenesis, which causes a poor survival outcome for the treated patients. The laboratory of Peter Carmeliet is focusing on the intracellular (metabolic) adaptation of endothelial cells (ECs) during angiogenesis. ECs are the building blocks of blood vessels and EC proliferation underlies blood vessel formation. Ongoing studies show that there is a metabolic switch underlying angiogenesis (K. De Bock et al, resubmitted to Cell). So, instead of/in addition to targeting tumor cells, we propose to target EC metabolism,  reventing ECs to initiate proliferation and blood vessel formation. This project aims at understanding these metabolic changes in order to develop novel therapeutic strategies to block angiogenesis.