Artikel
Microglia as a therapeutical target in malignant gliomas
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Autoren
Veröffentlicht: | 8. Juni 2016 |
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Gliederung
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Objective: Analysis of temozolomide, dexamethasone and minocycline on pro-tumorigenic properties of glioma infiltrating microglia (GIM) in mouse and human cell and tissue culture experimental models.
Method: We used RT-PCR, qPCR, ELISA and immunohistochemistry in mouse primary microglia cultures or in human glioma infiltrating CD11b+ cells (MACS sorted from human GBM samples) or in human glioblastoma tissue cultures to test effects of temozolomide, dexamethasone and minocycline on microglia properties important for glioma invasiveness, survival and immunosuppression.
Results: Using primary microglia and GIM we demonstrate that minocycline and dexamethasone or their combination reduce glioma stimulated microglial proliferation and diminish survival of microglia by inducing apoptosis. Moreover, minocycline and dexamethasone down-regulate release of active matrix metalloproteinase 2 (MMP-2) from glioma stimulated microglia. Further, we determined diminished secretion of IL-10 in microglia treated with minocycline and dexamethasone. Finally in a human glioblastoma tissue culture we confirm the effect of minocycline, dexamethasone and temozolomide to reduce proliferation of microglia and induce apoptosis in glioma cells.
Conclusions: Minocycline and dexamethasone treatment of mouse primary microglia and human GIM down-regulates microglial proliferation, MMP-2 activation and immunosuppression. Minocycline and dexamethasone are promising candidates for novel glioblastoma therapy by inhibiting microglial properties that promote glioblastoma development.