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. 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 (13C) after 13C-glutamine infusion. 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. Thus, our results outline the specific enhanced glutamine flux in vivo of the aggressive mesenchymal GBM subtype.

中文翻译：

---

人间充质胶质母细胞瘤在原位小鼠模型中的谷氨酰胺摄取和利用

胶质母细胞瘤 (GBM) 在细胞和分子基础上具有高度异质性。有人提出，从人类肿瘤建立的原代细胞的谷氨酰胺代谢将侵袭性间充质 GBM 亚型与其他亚型区分开来。为了研究体内谷氨酰胺代谢，我们使用人类原位小鼠模型进行 GBM。使用质谱分析从植入的表达不同分子特征的原代 GBM 细胞演变而来的肿瘤的代谢物库和 13C-谷氨酰胺输注后碳 13 (13C) 的富集。我们的研究结果表明，与对照脑组织和其他 GBM 亚型相比，间充质 GBM 肿瘤的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。因此，