Endothelial metabolic reprogramming influences tumor immune microenvironment

Figure 2 Metabolism of tumor endothelial cells. Tumor endothelial cell (TEC) exhibits higher levels of glycolysis than normal endothelial cell. 6-phosphofructo-2-kinase/fructose-2,6-bisphosph-atase 3, an activator of glycolysis, is overexpressed in TEC. Endothelial cells transport fatty acids into mitochondria via carnitine palmitoyltransferase 1A. In proliferating endothelial cells, carnitine palmitoyltransferase 1A is the rate-limiting enzyme for fatty acid oxidation and fatty acid oxidation provides a significant amount of substrate for deoxy nucleotide triphosphate synthesis. Enhanced glutamine metabolism in TEC provides amino acid substrates for nucleotide and biomass synthesis. Additionally, serine can be synthesized directly from 3-phosphoglycerate, which is produced by glycolysis, via serine synthesis pathway. Compared to normal blood vessels, tumor blood vessels have a disrupted barrier and distorted structure. They are more likely to develop hypoxia and metabolic abnormalities, which promote the dissemination of tumor cells. TEC: Tumor endothelial cell; PFKFB3: 6-phosphofructo-2-kinase/fructose-2,6-bisphosph-atase 3; HK2: Hexokinase 2; PPP: Pentose phosphate pathway; SSP: Serine synthesis pathway; PHGDH: Phosphoglycerate dehydrogenase; PSAT1: Phosphoserine aminotransferase 1; FASN: Fatty acid synthase; FAs: Fatty acids; FAO: Fatty acid oxidation; CPT1a: Carnitine palmitoyltransferase 1a; dNTP: Deoxy nucleotide triphosphate; TCA: Tricarboxylic acid; α-KG: Α-ketoglutarate; Glu: Glutamate; Gln: Glutamine; GLS1: Glutaminase 1; OXPHOS: Oxidative phosphorylation; ASNS: Asparagine synthetase.