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

D-type cyclins control the anti-tumourigenic response of neural precursor cells against gliomas

D-Typ Cycline steuern die anti-tumorigene Wirkung neuronaler Vorläuferzellen auf Glioblastome

Meeting Abstract

  • corresponding author M. Synowitz - Cellular Neuroscience Group, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • J.-H. Waelzlein - Cellular Neuroscience Group, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • B. Kaminska - Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland
  • U. Nuber - Medical Faculty, University of Lund, Sweden
  • H. Kettenmann - Cellular Neuroscience Group, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • R. Glass - Cellular Neuroscience Group, 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. DocFR.09.04

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc125.shtml

Veröffentlicht: 11. April 2007

© 2007 Synowitz et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Adult neurogenesis takes place in two germinative centres of the brain, the subventricular zone (SVZ) and the dentate gyrus. In a previous study we demonstrated that neural precursor cells (NPCs) are attracted towards glioblastomas and have strong anti-tumourigenic effects by inducing glioblastoma cell death. The increase in malignancy with age correlates with the age-dependent decline of NPCs in the brain. To study the influence of glioblastoma cells on NPC properties, we compared microarrays from NPCs alone or in coculture with glioblastoma cells.

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-out mice are the methodical base.

Results: We observed an upregulation of several mitosis-related genes, especially of cyclin D1. RT-PCR of microdissected SVZ and immunohistochemistry of identified NPCs revealed that cyclin D1 and D2 are present in the SVZ of young (P30) mice, but only cyclin D2 remains expressed in fully adult (P90) animals. Cyclin D3 was virtually absent from the SVZ of P30 and P90 animals. P30 mice maintained the expression of cyclin D1 and D2 during tumour growth in the hemisphere ipsi- and contralateral to the tumour. Mice of P90 showed some reexpression of cyclin D1 in the ipsilateral hemisphere concomitant with a strong upregulation of p21 (waf1), a tumour suppressor protein regulated by p53, specifically in the tumour-exposed SVZ. As cyclin D2 is the predominant D-type cyclin in fully adult animals and is therefore exclusively responsible for adult neurogenesis, cyclin D2 knockout animals have few proliferating NPCs. Glioma injection into cyclin D2 (-/-) mice resulted in increased tumour size in both P30 and P90 mice as compared to wildtype animals.

Conclusions: We conclude that cell proliferation is necessary to recruit sufficient NPCs towards gliomas to mediate an anti-tumourigenic effect. NPCs in older animals have decreased proliferative potential due to a lack of cyclin D1 and even the attempt to re-express cyclin D1 is counteracted by a simultaneous rise in p21 (waf1).

(The first two authors equally contributed to this work)