PPAR Gamma Activators: Off-Target Against Glioma Cell Migration and Brain Invasion
Figure 3
Δ2-Troglitazone inhibits
glioma progression in an organotypic glioma transplantation model. (a) Organotypic hippocampal glioma
invasion assay was performed as described earlier [10, 12, 30]. In brief, enhanced green
fluorescent protein (eGFP) positive F98 rat glioma cells were transplanted into
the entorhinal cortex of organotypic rat brain slice cultures one day after preparation. DAI
= days after implantation. DG = dentate gyrus. EC = entorhinal cortex. (b) Tumor progression was monitored by fluorescent
microscopy over the time course of 12 days. Quantification of the tumor
infiltration area at day 1 to day 12 after transplantation derived from 3
independent experiments is shown. For each experiment, the tumor infiltration
area at DAI 1 was defined as 100%. Data are given as mean ± SD percentage. At
DAI 12, the tumor infiltration area significantly increased to 448 ± 71 % (, -test) in solvent-matched controls but
remained unchanged following Δ2-TRO treatment (75 ± 22 %; , -test). Starting from DAI 2,
differences in tumor progression (TRO versus Δ2-TRO) reached
statistical significance (, -test) (c) A
continuous increase of the bulk tumor masses was observed in solvent-matched
controls while 10 M concentrations of Δ2-TRO effectively
blocked tumor progression. Right column: magnification of the indicated border
area between bulk tumor mass and rat brain tissue. In controls, F98 glioma
cells have diffusely migrated into the adjacent brain parenchyma, while a sharp
tumor border was observed following Δ2-TRO treatment (scale bar: 200 m).
