Glutamine uptake and utilization of human mesenchymal glioblastoma in orthotopic mouse model.

IF 6 3区医学 Q1 CELL BIOLOGY

Cancer & Metabolism Pub Date : 2020-08-10 eCollection Date: 2020-01-01 DOI:10.1186/s40170-020-00215-8

Kristell Oizel, Chendong Yang, Ophelie Renoult, Fabien Gautier, Quyen N Do, Noemie Joalland, Xiaofei Gao, Bookyung Ko, François Vallette, Woo-Ping Ge, François Paris, Ralph J DeBerardinis, Claire Pecqueur

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Abstract

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 (¹³C) after ¹³C-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.

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人间质胶质母细胞瘤对谷氨酰胺的摄取和利用（正位小鼠模型）。

背景：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，从人类肿瘤中提取的原代细胞的谷氨酰胺代谢可区分侵袭性间质 GBM 亚型和其他亚型：方法：为了研究谷氨酰胺的体内代谢，我们使用了人类 GBM 正位小鼠模型。结果：我们的研究结果表明，间质GBM亚型中，谷氨酰胺的含量最高，而其他亚型中，谷氨酰胺的含量最低：结果：我们的研究结果表明，与对照脑组织和其他 GBM 亚型相比，间质 GBM 肿瘤对谷氨酰胺的摄取和利用都有所增加。此外，谷氨酰胺合成酶和转谷氨酰胺酶-2的表达与GBM代谢表型相应：因此，我们的研究结果概述了侵袭性间质 GBM 亚型体内谷氨酰胺通量的特异性增强。

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来源期刊

Cancer & Metabolism Multiple-

自引率

1.70%

发文量

审稿时长

14 weeks

期刊介绍： Cancer & Metabolism welcomes studies on all aspects of the relationship between cancer and metabolism, including: -Molecular biology and genetics of cancer metabolism -Whole-body metabolism, including diabetes and obesity, in relation to cancer -Metabolomics in relation to cancer; -Metabolism-based imaging -Preclinical and clinical studies of metabolism-related cancer therapies.