原位小鼠模型中人间质胶质母细胞瘤的谷氨酰胺摄取与利用
Glutamine uptake and utilization of human mesenchymal glioblastoma in orthotopic mouse model.
作者信息
Oizel Kristell, Yang Chendong, Renoult Ophelie, Gautier Fabien, Do Quyen N, Joalland Noemie, Gao Xiaofei, Ko Bookyung, Vallette François, Ge Woo-Ping, Paris François, DeBerardinis Ralph J, Pecqueur Claire
机构信息
Children's Research Institute, UT Southwestern Medical Center, Dallas, TX 75390 USA.
Université de Nantes, CNRS, INSERM, CRCINA, Nantes, France.
出版信息
Cancer Metab. 2020 Aug 10;8:9. doi: 10.1186/s40170-020-00215-8. eCollection 2020.
BACKGROUND
Glioblastoma (GBM) are highly heterogeneous on the cellular and molecular basis. It has been proposed that glutamine metabolism of primary cells established from human tumors discriminates aggressive mesenchymal GBM subtype to other subtypes.
METHODS
To study glutamine metabolism in vivo, we used a human orthotopic mouse model for GBM. Tumors evolving from the implanted primary GBM cells expressing different molecular signatures were analyzed using mass spectrometry for their metabolite pools and enrichment in carbon 13 (C) after C-glutamine infusion.
RESULTS
Our results showed that mesenchymal GBM tumors displayed increased glutamine uptake and utilization compared to both control brain tissue and other GBM subtypes. Furthermore, both glutamine synthetase and transglutaminase-2 were expressed accordingly to GBM metabolic phenotypes.
CONCLUSION
Thus, our results outline the specific enhanced glutamine flux in vivo of the aggressive mesenchymal GBM subtype.
背景
胶质母细胞瘤（GBM）在细胞和分子水平上具有高度异质性。有人提出，从人类肿瘤中建立的原代细胞的谷氨酰胺代谢可将侵袭性间充质GBM亚型与其他亚型区分开来。
方法
为了研究体内谷氨酰胺代谢，我们使用了GBM的人原位小鼠模型。对植入的表达不同分子特征的原发性GBM细胞演变而来的肿瘤进行质谱分析，以检测其代谢物池以及在注入13C-谷氨酰胺后碳13（C）的富集情况。
结果
我们的结果表明，与对照脑组织和其他GBM亚型相比，间充质GBM肿瘤显示出谷氨酰胺摄取和利用增加。此外，谷氨酰胺合成酶和转谷氨酰胺酶-2均根据GBM代谢表型表达。
结论
因此，我们的结果概述了侵袭性间充质GBM亚型在体内特定增强的谷氨酰胺通量。
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