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Heterogeneity of Amino Acid Profiles of Proneural and Mesenchymal Brain-Tumor Initiating Cells.
Seliger, Corinna; Rauer, Lisa; Wüster, Anne-Louise; Moeckel, Sylvia; Leidgens, Verena; Jachnik, Birgit; Ammer, Laura-Marie; Heckscher, Simon; Dettmer, Katja; Riemenschneider, Markus J; Oefner, Peter J; Proescholdt, Martin; Vollmann-Zwerenz, Arabel; Hau, Peter.
Afiliación
  • Seliger C; Department of Neurology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
  • Rauer L; Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, 93053 Regensburg, Germany.
  • Wüster AL; Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, 93053 Regensburg, Germany.
  • Moeckel S; Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Freiburg, 79104 Freiburg, Germany.
  • Leidgens V; Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, 93053 Regensburg, Germany.
  • Jachnik B; Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, 93053 Regensburg, Germany.
  • Ammer LM; Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, 93053 Regensburg, Germany.
  • Heckscher S; Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, 93053 Regensburg, Germany.
  • Dettmer K; Institute of Functional Genomics, University of Regensburg, 93053 Regensburg, Germany.
  • Riemenschneider MJ; Institute of Functional Genomics, University of Regensburg, 93053 Regensburg, Germany.
  • Oefner PJ; Department of Neuropathology, University Hospital Regensburg, 93053 Regensburg, Germany.
  • Proescholdt M; Institute of Functional Genomics, University of Regensburg, 93053 Regensburg, Germany.
  • Vollmann-Zwerenz A; Department of Neurosurgery, University Hospital Regensburg, 93053 Regensburg, Germany.
  • Hau P; Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, 93053 Regensburg, Germany.
Int J Mol Sci ; 24(4)2023 Feb 06.
Article en En | MEDLINE | ID: mdl-36834608
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Glioblastoma / Metformina Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Glioblastoma / Metformina Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza