Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Kidney Cancer Program, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Cell Metab. 2018 Nov 6;28(5):793-800.e2. doi: 10.1016/j.cmet.2018.07.020. Epub 2018 Aug 23.
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 C-labeled fuels in ccRCC patients and compared labeling patterns in tumors and adjacent kidney. After infusion with [U-C]glucose, ccRCCs displayed enhanced glycolytic intermediate labeling, suppressed pyruvate dehydrogenase flow, and reduced TCA cycle labeling, consistent with the Warburg effect. Comparing C 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 C infusions, ccRCC is the first to demonstrate a convincing shift toward glycolytic metabolism.
透明细胞肾细胞癌（ccRCC）是最常见的人类肾癌类型。组织学和分子分析表明，ccRCC 的代谢发生了显著改变。最近对肺癌和颅内恶性肿瘤的人体研究表明，三羧酸（TCA）循环中的碳水化合物氧化出乎意料地得到了保留。为了测试 ccRCC 氧化 TCA 循环底物的能力，我们给 ccRCC 患者输注了[U-C]标记的燃料，并比较了肿瘤和相邻肾脏中的标记模式。输注[U-C]葡萄糖后，ccRCC 显示出增强的糖酵解中间产物标记、抑制的丙酮酸脱氢酶流和减少的 TCA 循环标记，与瓦博格效应一致。比较 ccRCC、脑和肺肿瘤之间的 C 标记显示出显著的差异。原发性 ccRCC 肿瘤表现出最高的糖酵解中间产物富集和最低的 TCA 循环中间产物富集。在通过术中 C 输注分析的人类肿瘤中，ccRCC 是第一个表现出向糖酵解代谢明显转变的肿瘤。
