Glutamine uptake and utilization of human mesenchymal glioblastoma in orthotopic mouse model
Kristell Oizel, Chendong Yang, Ophélie Renoult, Fabien Gautier, N. Quyen, Noémie Joalland, Xiaofei Gao, Bookyung Ko, François M. Vallette, Woo‐Ping Ge, François Paris, Ralph J. DeBerardinis, Claire Pecqueur
Abstract
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 ( 13 C) after 13 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.