Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA.
Cancer Res. 2013 Jan 15;73(2):529-38. doi: 10.1158/0008-5472.CAN-12-3461. Epub 2012 Nov 30.
Renal cell carcinomas (RCC) are a heterogeneous group of tumors with a wide range of aggressiveness. Noninvasive methods to confidently predict the tumor biologic behavior and select appropriate treatment are lacking. Here, we investigate the dynamic metabolic flux in living RCC cells using hyperpolarized (13)C-pyruvate magnetic resonance spectroscopy (MRS) combined with a bioreactor platform and interrogated the biochemical basis of the MRS data with respect to cancer aggressiveness. RCC cells have significantly higher pyruvate-to-lactate flux than the normal renal tubule cells. Furthermore, a key feature distinguishing the localized from the metastatic RCC cells is the lactate efflux rate, mediated by the monocarboxylate transporter 4 (MCT4). The metastatic RCC cells have significantly higher MCT4 expression and corresponding higher lactate efflux, which is essential for maintaining a high rate of glycolysis. We show that such differential cellular transporter expression and associated metabolic phenotype can be noninvasively assessed via real-time monitoring of hyperpolarized (13)C-pyruvate-to-lactate flux.
肾细胞癌（RCC）是一组具有广泛侵袭性的异质性肿瘤。目前缺乏能够有信心地预测肿瘤生物学行为并选择合适治疗方法的非侵入性方法。在这里，我们使用 13C- 丙酮酸磁共振波谱（MRS）结合生物反应器平台来研究活的 RCC 细胞中的动态代谢通量，并根据癌症侵袭性来研究 MRS 数据的生化基础。RCC 细胞的丙酮酸到乳酸通量明显高于正常肾小管细胞。此外，区分局限性和转移性 RCC 细胞的一个关键特征是由单羧酸转运蛋白 4（MCT4）介导的乳酸外排率。转移性 RCC 细胞的 MCT4 表达明显更高，相应的乳酸外排率也更高，这对于维持高糖酵解率是必不可少的。我们表明，通过实时监测 13C- 丙酮酸到乳酸的通量，可以非侵入性地评估这种差异细胞转运蛋白表达和相关的代谢表型。
