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Minocycline reduces glioma expansion and invasion by attenuating microglial MT1-MMP expression

Item Type:Article
Title:Minocycline reduces glioma expansion and invasion by attenuating microglial MT1-MMP expression
Creators Name:Markovic, D.S. and Vinnakota, K. and van Rooijen, N. and Kiwit, J. and Synowitz, M. and Glass, R. and Kettenmann, H.
Abstract:Glioma cells release soluble factors, which induce the expression of membrane type 1 matrix metalloprotease (MT1-MMP) in tumor associated microglia and then exploit MT1-MMP mediated matrix degradation for invasion. Here, we show that minocycline blocked the increase in MT1-MMP expression and activity in cultivated microglia stimulated with glioma conditioned medium. Glioma growth within an organotypic brain slice preparation was reduced by minocycline and this reduction depended on the presence of microglia. Glioma growth in an experimental mouse model was strongly reduced by the addition of minocycline to drinking water, compared to untreated controls. Coherently, we observed in our orthotopic glioma implantation model, that MT1-MMP was abundantly expressed in glioma associated microglia in controls, but was strongly attenuated in tumors of minocycline treated animals. Overall, our study indicates that the clinically approved antibiotic minocycline is a promising new candidate for adjuvant therapy against malignant gliomas.
Keywords:Minocycline, Microglia, Glioma, MT1-MMP, Animals, Mice
Source:Brain Behavior and Immunity
Publisher:Academic Press
Page Range:624-628
Date:May 2011
Official Publication:https://doi.org/10.1016/j.bbi.2011.01.015
PubMed:View item in PubMed

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