Metabolic remodeling in human colorectal cancer and surrounding tissues: alterations in regulation of mitochondrial respiration and metabolic fluxes.

摘要: The aim of the work was to evaluate whether or not there is glycolytic reprogramming in neighboring cells colorectal cancer (CRC). Using postoperative material we have compared functional capacity oxidative phosphorylation (OXPHOS) CRC cells, their activity and inclination aerobic glycolysis, with those surrounding healthy colon tissue cells. Experiments showed that human cannot be considered a hypoxic tumor, since malignancy itself it exhibited even higher rates OXPHOS than large intestine. absence acute hypoxia carcinomas also confirmed by practically equal glucose-phosphorylating as non-tumorous upregulation VEGF family ligands. Studies indicated vivo exert strong distant effect on energy metabolism so they acquire bioenergetic parameters specific tumor itself. growth associated potent downregulation creatine kinase system. As tissue, display high values basal ADP activated respiration rates. Strong differences between normal affinity mitochondria for were revealed; corresponding Km measured 93.6±7.7 µM 84.9±9.9 nearby tissue; both these apparent (ADP) considerably (by almost 3 times) lower comparison (256±34 µM).