gms | German Medical Science

65th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

11 - 14 May 2014, Dresden

Endogenous neural precursor cells accumulate at tumors of the human brain and induce cell death of high-grade gliomas

Meeting Abstract

  • Rainer Glass - Neurochirurgische Forschung, Neurochirurgie, Klinik der Universität München
  • Kristin Stock - Zelluläre Neurowissenschaften, Max Delbrück Centrum (MDC) Berlin
  • Jadranka Macas - DKTK, Neurologisches Institut (Edinger Institute), DKFZ, Universitätsklinikum Frankfurt/M.
  • Helmut Kettenmann - Zelluläre Neurowissenschaften, Max Delbrück Centrum (MDC) Berlin
  • Stefan Momma - DKTK, Neurologisches Institut (Edinger Institute), DKFZ, Universitätsklinikum Frankfurt/M.
  • Michael Synowitz - Zelluläre Neurowissenschaften, Max Delbrück Centrum (MDC) Berlin; Neurochirurgie, Charité – Universitätsmedizin Berlin, Berlin

Deutsche Gesellschaft für Neurochirurgie. 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Dresden, 11.-14.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocDI.16.02

doi: 10.3205/14dgnc219, urn:nbn:de:0183-14dgnc2192

Published: May 13, 2014

© 2014 Glass et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Data from mouse models suggest that high-grade gliomas (HG-gliomas) originale from somatic mutant neural stem and precursor cells (NPCs). We found that endogenous NPCs also defend the brain against HG-gliomas. Here, we describe the signal transduction mechanism of NPC-mediated tumor suppression and present data on the tropism of endogenous NPCs to human HG-gliomas.

Method: For our experiments we used transgenic mouse models, human HG-glioma biopsies, molecular biology techniques (microarrays, real-time PCR, mass-spectrometry, array-CGH, fluorescence in situ hybridization), cell-culture (primary NPC- and glioma cultures of human and murine origin), immunohistochemistry and survival studies in orthotopic mouse tumor models.

Results: NPCs migrate from the subventricular zone to HG-gliomas, reduce glioma expansion and prolong survival by releasing a group of fatty acid ethanolamides that have agonistic activity on the vanilloid receptor (transient receptor potential vanilloid subfamily member-1; TRPV1). TRPV1 expression is much higher in HG-gliomas than in tumor-free brain and TRPV1 stimulation triggers tumor cell death. NPC-mediated tumor suppression can be mimicked in the adult brain by the systemic administration of synthetic vanilloids suggesting that TRPV1 agonists hold potential as new HG-astrocytoma therapeutics. Furthermore, we analyzed the tumor-parenchyma interface of neurosurgical resections for the presence of NPCs. We observed that PSA-NCAM-positive NPCs, which are genetically distinct from the the tumor mass, accumulate at the border of high-grade gliomas and display a marker profile consistent with immature migratory neural progenitors.

Conclusions: Overall, our data reveal that NPCs are attracted to high-grade gliomas in humans, that NPCs suppress HG-gliomas in tumor models and that NPC-released anti-tumorigenic factors can be used inpre-clinical HG-glioma therapy.