Multiplexed Single-Cell Measurements of FDG Uptake and Lactate Release Using Droplet Microfluidics
Multiplexed Single-Cell Measurements of FDG Uptake and Lactate Release Using Droplet Microfluidics
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DOI：
10.1177/1533033819841066
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发表时间：
2019-03-29
影响因子：
2.8
通讯作者：
Pratx, Guillem
中科院分区：
文献类型：
--
作者：
Sengupta, Debanti;Mongersun, Amy;Pratx, Guillem
前言：葡萄糖利用和乳酸释放是肿瘤代谢的两个重要指标。大多数肿瘤消耗葡萄糖和释放乳酸的速率高于正常组织，这是由于有氧糖酵解增强。然而，这两个代谢指标以前没有在同一细胞中的单细胞水平上进行过研究。目的：开发和表征一种新型液滴微流体装置，用于在封装在油包水液滴阵列中的单个活细胞中多重测量葡萄糖摄取（通过其类似物F-18-氟脱氧葡萄糖）和乳酸盐释放。结果如下：令人惊讶的是，F-18-氟脱氧葡萄糖摄取和乳酸盐释放在单细胞水平上仅略微相关，即使在标准细胞系（MDA-MB-231）中测定时也是如此。虽然F-18-氟脱氧葡萄糖亲合细胞释放大量的乳酸，但相反的情况并非如此，许多细胞释放大量的乳酸而不吸收F-18-氟脱氧葡萄糖。讨论内容：这些结果证实，除了有氧糖酵解之外，癌细胞还依赖于多种代谢途径，并且即使在受控的培养条件下，这些途径的使用也是高度异质的。在临床上，大的细胞间变异性表明，F-18-氟脱氧葡萄糖摄取的正电子发射断层扫描测量仅代表总体意义上的代谢通量，而不是肿瘤内的单个癌细胞。
Introduction: Glucose utilization and lactate release are 2 important indicators of cancer metabolism. Most tumors consume glucose and release lactate at a higher rate than normal tissues due to enhanced aerobic glycolysis. However, these 2 indicators of metabolism have not previously been studied on a single-cell level, in the same cell. Objective: To develop and characterize a novel droplet microfluidic device for multiplexed measurements of glucose uptake (via its analog F-18-fluorodeoxyglucose) and lactate release, in single live cells encapsulated in an array of water-in-oil droplets. Results: Surprisingly, F-18-fluorodeoxyglucose uptake and lactate release were only marginally correlated at the single-cell level, even when assayed in a standard cell line (MDA-MB-231). While F-18-fluorodeoxyglucose-avid cells released substantial amounts of lactate, the reverse was not true, and many cells released high amounts of lactate without taking up F-18-fluorodeoxyglucose. Discussion: These results confirm that cancer cells rely on multiple metabolic pathways in addition to aerobic glycolysis and that the use of these pathways is highly heterogeneous, even under controlled culture conditions. Clinically, the large cell-to-cell variability suggests that positron emission tomography measurements of F-18-fluorodeoxyglucose uptake represent metabolic flux only in an aggregate sense, not for individual cancer cells within the tumor.