Tumor metabolism: cancer cells give and take lactate.
Tumors contain well-oxygenated (aerobic) and poorly oxygenated (hypoxic) regions, which were thought to utilize glucose for oxidative and glycolytic metabolism, respectively. In this issue of the JCI, Sonveaux et al. show that human cancer cells cultured under hypoxic conditions convert glucose to lactate and extrude it, whereas aerobic cancer cells take up lactate via monocarboxylate transporter 1 (MCT1) and utilize it for oxidative phosphorylation (see the related article beginning on page 3930). When MCT1 is inhibited, aerobic cancer cells take up glucose rather than lactate, and hypoxic cancer cells die due to glucose deprivation. Treatment of tumor-bearing mice with an inhibitor of MCT1 retarded tumor growth. MCT1 expression was detected exclusively in nonhypoxic regions of human cancer biopsy samples, and in combination, these data suggest that MCT1 inhibition holds potential as a novel cancer therapy.
Semenza
Gregg L
GL
Vascular Program, Institute for Cell Engineering, Department of Pediatrics, John Hopkins University School of Medicine, Baltimore, Maryland, USA. gsemenza@jhmi.edu
D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D027501:Monocarboxylic Acid Transporters / Q000096:biosynthesis* / Q000235:genetics; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D014183:Transplantation, Heterologous; D000099233:Monocarboxylate Transport Protein 1
D005947:Glucose; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D010100:Oxygen; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1