Article
Microglia promote invasiveness of glioma cells in cultured brain slices
Mikroglia fördert das Wachstum glialer Hirntumore
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Published: | April 23, 2004 |
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Outline
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Objective
The strong invasiveness of glioma cells is a significant clinical problem and an important reason for the high mortality. Microglia, the immunocompetent cells of the brain, contribute significantly to the tumour mass and are potential interaction partners of the glioma cells. Here we studied the impact of the presence of microglia on tumour cell migration in cultured brain slices.
Methods
Cells from a rat glioma line (F98) were stably transfected with green- (pEGFP) or red-fluorescent protein (dsRed). Brain slices (n = 71) from mice (n = 10, 16 days old) were cultured for 4 days before about 5000 F98 dsRed or pEGFP cells were injected. We followed the migration of fluorescent cells over time using 2-photon microscopy. To deplete the slices from microglia, cultures were treated with clodronate-filled liposomes for 24 h. Clodronate induce apoptosis in the target cell. After an additional culture period of 72 h we were not longer able to detect labelled microglial cells, indicating that the slices were free of microglia. Astrocytes and neurons continued to survive as in controls.
Results
24 h after inoculation, tumour cells were found within a maximal distance of 400 µm to the center of the injection site. During the 4 following days, 45,84 ± 12,31 % of the tumour cells in untreated brain slices had migrated more than 500 µm. When glioma cells were injected into the microglia-depleted slices, the migration rate was significantly lower: Only 15,75 ± 1,77 % of tumour cells migrated more than 500 µm within 4 days. PBS-filled liposomes and untreated slices served as controls.
Conclusions
Our data indicate that microglia do not only fail to develop an effective immune response upon contact with brain tumours, but their presence promotes tumour invasiveness.