Artikel
Cellular Plasticity of endogenous neural precursors responding to glioblastomas
Glioblastom induzierte zelluläre Plastizität endogen neuronaler Stammzellen
Suche in Medline nach
Autoren
Veröffentlicht: | 4. Mai 2005 |
---|
Gliederung
Text
Objective
Nestin-positive cells are found within and around human glioblastomas and were thought to represent dedifferentiating cells originating from these tumors. We now demonstrate that these nestin expressing cells are neural progenitors cells from the subventricular zone, which migrate to the tumor and subsequently differentiate.
Methods
G261 glioblastoma cells stably expressing DsRed were injected into striatum of transgenic mice expressing green fluorescent protein under the nestin promoter. This mouse model allowed us to distinguish nestin-positive cells of the brain parenchyma from those generated by the tumor. Immunofluorescent triple labeling was carried out on 40-μm-free-floating sections using a spectral confocal microscope.
Results
14 days after injection nestin-positive cells in brains of 25 day old mice surrounded the glioblastoma with several cellular layers. The first nestin-positive cells were found at the tumor 4 days after injection, while the highest density was reached after 14 days. Tumors in young animals attracted more nestin-positive cells since the presence of neural progenitors declines with increasing age (comparing animals 100, 180 and 360 days of age). Nestin-positive cells co-expressed markers for progenitor cells (Musashi, TUC-4), immature neurons (doublecortin) and glial cells (NG-2,GFAP) and proliferated (Ki67). Patch-clamp studies indicated that cells expressed a current profile of immature glial cells. Markers for mature astrocytes and neurons (S-100β and β-tubulin) did not label nestin-positive cells. The progenitors originated from the subventricular zone, since intraventricular administration of DiI prior to tumour inoculation resulted in DiI stained nestin-positive cells surrounding the tumour. BrdU labelling indicated that the nestin-positive cells had previously divided. Moreover, in explant cultures from the subventricular zone precursor cells showed extensive tropism for glioblastoma aggregates.
Conclusions
Our data indicate that glioblastomas attract endogenous neural progenitor cells from the subventricular zone, which expressed markers of early, non-committed and of committed precursors.