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

Kristell Oizel (1) , Chendong Yang (1) , Ophelie Renoult (2) , Fabien Gautier (3, 4) , Quyen N Do (1) , Noemie Joalland (5, 6) , Xiaofei Gao (1) , Bookyung Ko (1) , François Vallette (5, 4) , Woo-Ping Ge (1) , François Paris (2, 4) , Ralph J Deberardinis (7, 1) , Claire Pecqueur (2, 6)

1 University of Texas Southwestern Medical Center [Dallas]
2 CRCINA-ÉQUIPE 14 - Endothelium Radiobiology and Targeting
3 CRCINA-ÉQUIPE 8 - Stress Adaptation and Tumor Escape in Breast Cancer
4 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
5 CRCINA-ÉQUIPE 9 - Apoptosis and Tumor Progression
6 LabEX IGO Immunothérapie Grand Ouest
7 HHMI - Howard Hughes Medical Institute [Chevy Chase]

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.

Mots clés: Glioblastoma; Glutamine; Human primary cells; Mesenchymal; Metabolism; Molecular subtype; Orthotopic model.

Domaines: Cancer

Kristell Oizel, Chendong Yang, Ophelie Renoult, Fabien Gautier, Quyen N Do, et al.. Glutamine uptake and utilization of human mesenchymal glioblastoma in orthotopic mouse model. Cancer and Metabolism, 2020, 8, pp.9. ⟨10.1186/s40170-020-00215-8⟩. ⟨inserm-03013555⟩