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

原位小鼠模型中人间充质胶质母细胞瘤的谷氨酰胺摄取和利用

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作者: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

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.

Conclusion

Thus, our results outline the specific enhanced glutamine flux in vivo of the aggressive mesenchymal GBM subtype.

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.

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