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The antitumorigenic response of neural precursors depends on subventricular proliferation and age

Item Type:Article
Title:The antitumorigenic response of neural precursors depends on subventricular proliferation and age
Creators Name:Walzlein, J.H. and Synowitz, M. and Engels, B. and Markovic, D.S. and Gabrusiewicz, K. and Nikolaev, E. and Yoshikawa, K. and Kaminska, B. and Kempermann, G. and Uckert, W. and Kaczmarek, L. and Kettenmann, H. and Glass, R.
Abstract:Glioblastomas, the most aggressive primary brain tumors, occur almost exclusively in adult patients. Neural precursor cells (NPCs) are anti-tumorigenic in mice, as they can migrate to glioblastomas and induce tumor cell death. Here, we show that the anti-tumor effect of NPCs is age-dependently controlled by cell proliferation in the subventricular zone (SVZ) and that NPCs accumulating at a glioblastoma are diverted from their normal migratory path to the olfactory bulb. Experimentally induced cortical glioblastomas resulted in decreased subventricular proliferation in adult (postnatal day 90), but not in young (postnatal day 30) mice. Adult mice supplied less NPCs to glioblastomas and had larger tumors than young mice. Apart from the difference in proliferation, there was neither a change in cell number and death-rate in the SVZ nor in angiogenesis and immune cell-density in the tumors. The ability to kill glioblastomas was similar in NPCs isolated from young and adult mice. The proliferative response of NPCs to glioblastomas depended on the expression of D-type cyclins. In young mice, NPCs express the cyclins D1 and D2, but the expression of cyclin D1 is lost during aging and in adult NPCs only cyclin D2 remains. In young and adult cyclin D2-deficient mice we observed a reduced supply of NPCs to glioblastomas and the generation of larger tumors, as compared to wild-type mice. We conclude that cyclin D1 and D2 are non-redundant for the antitumor response of subventricular NPCs. Loss of a single D-type cyclin results in a smaller pool of proliferating NPCs, lower number of NPCs migrating to the tumor and reduced anti-tumor activity.
Keywords:CNS Neoplasms, Tissue Maintenance, Stem and Precursor Cells of the CNS, Tumor Microenvironment, Animals, Mice
Source:Stem Cells
Publisher:AlphaMed Press
Page Range:2945-2954
Date:November 2008
Official Publication:https://doi.org/10.1634/stemcells.2008-0307
PubMed:View item in PubMed

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