Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth
Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth
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DOI：
10.7554/elife.53618
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发表时间：
2020-06-23
期刊：
影响因子：
7.7
通讯作者：
Meylan, Etienne
中科院分区：
文献类型：
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作者：
Contat, Caroline;Ancey, Pierre-Benoit;Meylan, Etienne
葡萄糖利用在肿瘤中增加，这是一种代谢过程，通过f -18氟脱氧葡萄糖正电子发射断层扫描（F-18-FDG-PET）在临床上观察到。然而，增加的葡萄糖摄取对肿瘤细胞是否重要？体内有哪些转运蛋白参与？在肺腺癌的基因工程小鼠模型中，我们发现在癌细胞中只缺失一种高表达的葡萄糖转运蛋白Glut1或Glut3并不会损害肿瘤的生长，而它们的联合缺失会减少肿瘤的发展。肿瘤的F-18-FDG-PET分析表明，Glut1和Glut3的丢失降低了葡萄糖摄取，而葡萄糖摄取主要依赖于Glut1。利用相关纳米级二次离子质谱（NanoSIMS）和电子显微镜的c -13-葡萄糖示踪，我们还报道了在肿瘤细胞中存在片状体样细胞器，这些细胞器部分依赖于Glut1积累葡萄糖来源的生物量。我们的研究结果表明，肺腺癌需要两种葡萄糖转运蛋白，对其双重阻断可以达到个体靶向无法达到的治疗效果。
Glucose utilization increases in tumors, a metabolic process that is observed clinically by F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one highly expressed glucose transporter, Glut1 or Glut3, in cancer cells does not impair tumor growth, whereas their combined loss diminishes tumor development. F-18-FDG-PET analyses of tumors demonstrate that Glut1 and Glut3 loss decreases glucose uptake, which is mainly dependent on Glut1. Using C-13-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we also report the presence of lamellar body-like organelles in tumor cells accumulating glucose-derived biomass, depending partially on Glut1. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma, the dual blockade of which could reach therapeutic responses not achieved by individual targeting.