Negative allosteric modulators of metabotropic glutamate receptor 3 target the stem-like phenotype of glioblastoma

Wirsching, Hans-Georg; Silginer, Manuela; Ventura, Elisa; Macnair, Will; Burghardt, Isabel; Claassen, Manfred; Gatti, Silvia; Wichmann, Jürgen; Riemer, Claus; Schneider, Hannah; Weller, Michael

doi:10.5167/uzh-206296

Citations

Citation copied

Wirsching, H.-G., Silginer, M., Ventura, E., Macnair, W., Burghardt, I., Claassen, M., Gatti, S., Wichmann, J., Riemer, C., Schneider, H., & Weller, M. (2021). Negative allosteric modulators of metabotropic glutamate receptor 3 target the stem-like phenotype of glioblastoma. Molecular Therapy : Oncolytics, 20, 166–174. https://doi.org/10.1016/j.omto.2020.12.009

Abstract

Glioblastoma is an invariably deadly disease. A subpopulation of glioma stem-like cells (GSCs) drives tumor progression and treatment resistance. Two recent studies demonstrated that neurons form oncogenic glutamatergic electrochemical synapses with post-synaptic GSCs. This led us to explore whether glutamate signaling through G protein-coupled metabotropic receptors would also contribute to the malignancy of glioblastoma. We found that glutamate metabotropic receptor (Grm)3 is the predominantly expressed Grm in glioblastoma. Associat