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| Item Type: | Article |
|---|---|
| Title: | The invasion promoting effect of microglia on glioblastoma cells is inhibited by cyclosporin A |
| Creators Name: | Sliwa, M., Markovic, D., Gabrusiewicz, K., Synowitz, M., Glass, R., Zawadzka, M., Wesolowska, A., Kettenmann, H. and Kaminska, B. |
| Abstract: | The invasion of tumour cells into brain tissue is a pathologic hallmark of WHO grades II-IV gliomas and contributes significantly to the failure of current therapeutic treatments. Activated microglial cells are abundant in brain tumours and may support tumour invasiveness. We have previously demonstrated that cyclosporin A (CsA) can affect growth of glioma cells in vitro by inhibiting signalling pathways, which are essential for tumour proliferation and invasiveness. In this work, we demonstrate that migration of EGFP-transfected glioblastoma cells in organotypic brain slices was significantly inhibited by treatment with CsA. On average 77% of untreated cells migrated beyond 500 microm, while only 28-33% cells migrated as far in the brain slices treated with CsA (P < 0.001). This inhibitory effect on glioblastoma invasion was lost when glioblastoma cells were injected into microglia-depleted brain slices. Moreover, CsA significantly inhibits intracranial glioma growth in vivo. We demonstrate that microglia-derived factors increase glioma invasiveness in Matrigel assay in vitro and this is associated with activation of the PI-3K/Akt signalling pathway. The invasion promoting effect of microglia is abolished in the presence of CsA. Furthermore, glioma-derived soluble factors induce morphological transformation of microglia and activate MAPK signalling, although production of pro-inflammatory factors was not observed. Our findings that CsA interferes at clinically relevant concentrations with the tumour-promoting role of microglia and impairs invasive growth of glioma cells in vivo may provide a novel therapeutic strategy against gliomas. |
| Keywords: | Cyclosporin A, Glioma Microenvironment, Invasiveness, Microglia, Signal Transduction, Animals, Mice, Rats |
| Source: | Brain |
| ISSN: | 0006-8950 |
| Publisher: | Oxford University Press |
| Volume: | 130 |
| Number: | Pt. 2 |
| Page Range: | 476-489 |
| Date: | 1 February 2007 |
| Official Publication: | https://doi.org/10.1093/brain/awl263 |
| PubMed: | View item in PubMed |
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