gms | German Medical Science

68th Annual Meeting of the German Society of Neurosurgery (DGNC)
7th Joint Meeting with the British Neurosurgical Society (SBNS)

German Society of Neurosurgery (DGNC)

14 - 17 May 2017, Magdeburg

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Targeting brain tumor stem cells by interfering with choline metabolism: Evidence for an EMT-choline oncometabolic network

Meeting Abstract

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  • Katharina Koch - Abt. Funktionelle Neurochirurgie und Stereotaxie, Neurochirurgische Universitätsklinik, Düsseldorf, Deutschland
  • Roland Hartmann - Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Juelich,, Jülich, Deutschland
  • Abigail Kora Suwala - Abt. Funktionelle Neurochirurgie und Stereotaxie, Neurochirurgische Universitätsklinik, Düsseldorf, Deutschland
  • Donata Maciaczyk - Abt. Funktionelle Neurochirurgie und Stereotaxie, Neurochirurgische Universitätsklinik, Düsseldorf, Deutschland
  • Dieter Willbold - Institute of Complex Systems (ICS-6) Structural Biochemistry, Forschungszentrum Juelich, Juelich, Germany., Jülich, Deutschland
  • Ulf Dietrich Kahlert - Abt. Funktionelle Neurochirurgie und Stereotaxie, Neurochirurgische Universitätsklinik, Düsseldorf, Deutschland
  • Jaroslaw Maciaczyk - Abt. Funktionelle Neurochirurgie und Stereotaxie, Neurochirurgische Universitätsklinik, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Society of British Neurological Surgeons. 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS). Magdeburg, 14.-17.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocMi.03.05

doi: 10.3205/17dgnc375, urn:nbn:de:0183-17dgnc3756

Published: June 9, 2017

© 2017 Koch et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Objective: Glioblastoma (GBM) is the most lethal primary brain tumor in adults with a median survival of less than two years. High levels of therapy resistance, strong cellular invasiveness and rapid cell growth demand aggressive multimodal therapies. Recent evidence has pointed to the existence of brain tumor stem cells (BTSCs), cells exhibiting stem cell properties which are thought to be responsible for tumor dissemination, relapse and chemo resistance. BTSCs have been associated with the expression of mesenchymal features as a result of epithelial-mesenchymal transition (EMT).

Methods: Using high resolution proton nuclear magnetic resonance spectroscopy (1H NMR) following dual metabolite extraction we analyzed the metabolism of GBM cell cultures both after EMT inhibition and differentiation of the cells to reduce stem cell character. Furthermore we compared metabolic response to different culture conditions and forced differentiation protocols.

Results: Induction of EMT and the stem cell character of GBM cells correlate with changes in their intracellular metabolome promoting cholinic phenotype, characterized by high intracellular levels of phosphocholine and total choline derivatives. Furthermore, interference with choline metabolism by targeting choline kinase alpha (CHKα) reversed EMT in GBM cells as we observed reduced invasiveness, clonogenicity, and expression of EMT associated genes.

Conclusion: Interfering with cellular metabolism could be a powerful strategy to suppress EMT and target chemo-resistant BTSCs through impairing their mesenchymal transdifferentiation. Moreover, the newly identified BTSC-oncometabolic network could be used to monitor the invasive properties of glioblastomas and the success of anti-BTSC therapy.