Cancer-Induced Metabolic Rewiring of Tumor Endothelial Cells

SIMPLE SUMMARY: Angiogenesis, the formation of new blood vessels from preexisting ones, is a complex and demanding biological process that plays an important role in physiological, as well as pathological conditions, including cancer. During tumor growth, the induction of angiogenesis allows tumor cells to grow, invade, and metastasize. Recent evidence supports endothelial cell metabolism as a critical regulator of angiogenesis. However, whether and how tumor endothelial cells rewire their metabolism in cancer remains elusive. In this review, we discussed the metabolic signatures of tumor endothelial cells and their symbiotic, competitive, and mechanical metabolic interactions with tumor cells. We also discussed the recent works that may provide a rationale for attractive metabolic targets and strategies for developing specific therapies against tumor angiogenesis. ABSTRACT: Cancer is a leading cause of death worldwide. If left untreated, tumors tend to grow and spread uncontrolled until the patient dies. To support this growth, cancer cells need large amounts of nutrients and growth factors that are supplied and distributed to the tumor tissue by the vascular system. The aberrant tumor vasculature shows deep morphological, molecular, and metabolic differences compared to the blood vessels belonging to the non-malignant tissues (also referred as normal). A better understanding of the metabolic mechanisms driving the differences between normal and tumor vasculature will allow the designing of new drugs with a higher specificity of action and fewer side effects to target tumors and improve a patient’s life expectancy. In this review, we aim to summarize the main features of tumor endothelial cells (TECs) and shed light on the critical metabolic pathways that characterize these cells. A better understanding of such mechanisms will help to design innovative therapeutic strategies in healthy and diseased angiogenesis.