gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Article

Send article

A subset of fast proliferating neural precursors suppress gliomas

Eine Untergruppe schnell prolifierender neuraler Vorläuferzellen hemmt das Wachstum experimenteller Glioblastome

Meeting Abstract

Search Medline for

  • corresponding author M. Synowitz - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • J.-H. Walzlein - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • B. Engels - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • K. Gabrusiewicz - Laboratory of Transcription Regulation, Dept. Cell Biology, Nencki Institute of Experimental Biology, Warsaw, Poland
  • M. Endres - Klinik und Poliklinik für Neurologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin
  • B. Kaminska - Laboratory of Transcription Regulation, Dept. Cell Biology, Nencki Institute of Experimental Biology, Warsaw, Poland
  • G. Kempermann - Neuronale Stammzellen, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland und Volkswagen Research Group, Experimentelle Neurologie, Klinik für Neurologie, Charité - Universitätsmedizin Berlin, Berlin
  • W. Uckert - Molekulare Zellbiologie und Gentherapie, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • L. Kaczmarek - Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland
  • H. Kettenmann - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • R. Glass - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 080

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2007/07dgnc335.shtml

Published: April 11, 2007

© 2007 Synowitz et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective: We recently discovered that neural precursor cells (NPCs) are recruited to experimental glioblastoma in large quantity and that NPCs exhibit anti-tumorigenic actions against glioblastoma. In our present study we used this model to get an insight into the mechanisms controlling precursor cell recruitment from the SVZ towards brain pathology. In particular, we investigated whether the supply of NPCs towards glioblastoma is controlled on the level of cell proliferation within the stem cell niche.

Methods: Retroviral tracing of NPCs, stereological quantification of proliferating cells in the subventricular zone (SVZ) by short BrdU pulses, RT-PCRs of microdissected SVZs and immunolabelling, and the use of cyclin D2 knock-outs mice are the methodical base.

Results: We show that the NPCs surrounding glioblastoma originate from rapidly proliferating cells in the subventricular zone (SVZ) and are diverted from their physiological migratory path towards the olfactory bulb thereby reducing olfactory bulb neurogenesis. In young mice (30 day old) high levels of subventricular proliferation maintained a continuous supply of NPCs, while in adult mice (90 day old) glioblastoma exhausted NPC proliferation in the SVZ. Fast proliferation of NPCs depended on the abundance of D-type cyclins, of which cyclin D1 age-dependently declined, accounting for the reduced supply of NPCs towards glioblastoma in adult. Disruption of the cyclin D2 gene specifically reduced adult neurogenesis and resulted in larger tumors.

Conclusions: We conclude that transit-amplifying cells in the SVZ maintain a steady supply of NPCs towards glioblastoma. Provision of NPCs to glioblastoma is limited by cell-autonomous and age-related mechanisms controlling precursor cell proliferation.

*Authors 1, 2, 10, 11 equally contributed to this work