Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo.
Cell Metab
; 28(5): 793-800.e2, 2018 11 06.
Article
en En
| MEDLINE
| ID: mdl-30146487
ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is the most common form of human kidney cancer. Histological and molecular analyses suggest that ccRCCs have significantly altered metabolism. Recent human studies of lung cancer and intracranial malignancies demonstrated an unexpected preservation of carbohydrate oxidation in the tricarboxylic acid (TCA) cycle. To test the capacity of ccRCC to oxidize substrates in the TCA cycle, we infused 13C-labeled fuels in ccRCC patients and compared labeling patterns in tumors and adjacent kidney. After infusion with [U-13C]glucose, ccRCCs displayed enhanced glycolytic intermediate labeling, suppressed pyruvate dehydrogenase flow, and reduced TCA cycle labeling, consistent with the Warburg effect. Comparing 13C labeling among ccRCC, brain, and lung tumors revealed striking differences. Primary ccRCC tumors demonstrated the highest enrichment in glycolytic intermediates and lowest enrichment in TCA cycle intermediates. Among human tumors analyzed by intraoperative 13C infusions, ccRCC is the first to demonstrate a convincing shift toward glycolytic metabolism.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Renales
/
Glucosa
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Neoplasias Renales
Límite:
Adult
/
Aged
/
Humans
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Middle aged
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos