Seliger, Corinna and Rauer, Lisa and Wuester, Anne-Louise and Moeckel, Sylvia and Leidgens, Verena and Jachnik, Birgit and Ammer, Laura-Marie and Heckscher, Simon and Dettmer, Katja and Riemenschneider, Markus J. and Oefner, Peter J. and Proescholdt, Martin and Vollmann-Zwerenz, Arabel and Hau, Peter (2023) Heterogeneity of Amino Acid Profiles of Proneural and Mesenchymal Brain-Tumor Initiating Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (4): 3199. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Glioblastomas are highly malignant brain tumors that derive from brain-tumor-initiating cells (BTICs) and can be subdivided into several molecular subtypes. Metformin is an antidiabetic drug currently under investigation as a potential antineoplastic agent. The effects of metformin on glucose metabolism have been extensively studied, but there are only few data on amino acid metabolism. We investigated the basic amino acid profiles of proneural and mesenchymal BTICs to explore a potential distinct utilization and biosynthesis in these subgroups. We further measured extracellular amino acid concentrations of different BTICs at baseline and after treatment with metformin. Effects of metformin on apoptosis and autophagy were determined using Western Blot, annexin V/7-AAD FACS-analyses and a vector containing the human LC3B gene fused to green fluorescent protein. The effects of metformin on BTICs were challenged in an orthotopic BTIC model. The investigated proneural BTICs showed increased activity of the serine and glycine pathway, whereas mesenchymal BTICs in our study preferably metabolized aspartate and glutamate. Metformin treatment led to increased autophagy and strong inhibition of carbon flux from glucose to amino acids in all subtypes. However, oral treatment with metformin at tolerable doses did not significantly inhibit tumor growth in vivo. In conclusion, we found distinct amino acid profiles of proneural and mesenchymal BTICs, and inhibitory effects of metformin on BTICs in vitro. However, further studies are warranted to better understand potential resistance mechanisms against metformin in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEWLY-DIAGNOSED GLIOBLASTOMA; STEM-CELLS; IN-VITRO; METFORMIN; CANCER; GLUCOSE; TEMOZOLOMIDE; METABOLISM; SENSITIVITY; INHIBITION; glioma; metabolism; metformin; proneural and mesenchymal brain-tumor-initiating cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Neurochirurgie Medicine > Lehrstuhl für Neurologie Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2024 08:48 |
| Last Modified: | 08 Mar 2024 08:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59042 |
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