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Microglia promote glioma migration
Ina Bettinger1, Solon Thanos, Werner Paulus
1Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, 48129 Münster, Germany.
Abstract:
Diffuse astrocytic gliomas extensively infiltrate brain tissue and contain numerous microglial cells, but it is unknown whether these two characteristic features are pathogenetically related. We therefore studied the effects of murine microglial cells on motility of GL261 mouse glioma cells using Boyden chamber assays. In the presence of microglia, glioma cell migration occurred earlier, and after 48 h it was threefold higher as compared to incubations without microglia. This effect was mediated by substances released from microglia, because similar effects were observed by microglia-conditioned medium, and it was specific to microglia, because oligodendroglia and endothelial cells only weakly stimulated glioma cell migration. Microglia activating substances (GM-CSF, LPS) led to a further increase of motility. These data support the notion that microglia accumulation in diffuse glial tumors does not merely represent a nonspecific reaction to tissue injury, but reflects participation of these cells in supporting and promoting the invasive phenotype of astrocytoma cells.
Insights
Microglia cells significantly enhance glioma cell migration in brain tumors. These findings suggest microglia actively promote astrocytoma invasion, not just react to injury.
Area of Science:
- Neuro-oncology
- Cell Biology
- Tumor Microenvironment
Background:
- Diffuse astrocytic gliomas infiltrate brain tissue and are characterized by the presence of microglial cells.
- The pathogenetic relationship between glioma infiltration and microglial cell accumulation remains unclear.
Purpose of the Study:
- To investigate the influence of murine microglial cells on the motility of GL261 mouse glioma cells.
- To determine if microglia actively contribute to the invasive properties of astrocytoma cells.
Main Methods:
- Boyden chamber assays were utilized to quantify glioma cell migration.
- Glioma cells were incubated with and without microglial cells or microglia-conditioned medium.
- The effect of microglial activating substances (GM-CSF, LPS) on glioma cell motility was assessed.
Main Results:
- Glioma cell migration was initiated earlier and increased threefold after 48 hours in the presence of microglia compared to controls.
- Microglia-conditioned medium replicated the stimulatory effect on glioma cell migration.
- Oligodendroglia and endothelial cells showed only weak stimulation of glioma cell migration, indicating specificity of the microglial effect.
- Microglia activating substances further augmented glioma cell motility.
Conclusions:
- Microglia actively promote the invasive phenotype of astrocytoma cells.
- Microglial accumulation in diffuse glial tumors is not merely a response to tissue damage but plays a functional role in tumor progression.