Endothelial glutamine metabolism : target for anti-tumor angiogenesis therapy.

Growing cancer cells rely on blood vessels for a continuous supply of nutrients and oxygen and secrete angiogenic growth factors to secure their own support. Consequently, inhibition of angiogenesis is a prime target in anti-cancer drug development. As traditional strategies, which rely on growth factor inhibition, are however confronted with toxicity and drug-resistance limitations, we will explore the alternative anti-angiogenesis strategy to "hit" the growth potential of the endothelial cells (EC) by altering their metabolism. We focus on metabolism of glutamine (Q), a key metabolite for cell proliferation in general. Our initial data indicate that Q deprivation prevents quiescent ECs from restarting proliferation. Using in vitro and in vivo expression, metabolic, and functional assays, we will i) characterize the Q metabolic fate and Q metabolic gene profile in quiescent versus proliferating ECs, and ii) explore targeting EC Q metabolism to inhibit tumor angiogenesis and suppress tumor growth.

Keywords:angiogenesis, cancer, glutamine, metabolism, endothelial

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences, Morphological sciences, Oncology, Cardiac and vascular medicine