Article

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

Max Delbrück Center for Molecular Medicine, Cellular Neuroscience, Robert Rössle Str. 10, 13125 Berlin, Germany.
Brain Behavior and Immunity (Impact Factor: 6.13). 02/2011; 25(4):624-8. DOI: 10.1016/j.bbi.2011.01.015
Source: PubMed

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.

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Available from: Katyayni Vinnakota, Dec 13, 2013
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    • "Induction of autophagic cell death may therefore help stop tumor development and optimize cancer treatment modalities (Ceteci et al. 2011; Guo et al. 2011; Chen et al. 2012). Interestingly, recent evidence indicates the clinically approved antibiotic minocycline, a highly lipid-soluble antibacterial known for its superior ability to cross the blood-brain barrier, to act as a promising new candidate for adjuvant therapy against malignant gliomas by reducing MT1-MMP expression (Markovic et al. 2011). More importantly, minocycline effectively inhibited tumor growth and induced autophagy in a xenograft tumor model of C6 glioma cells (Liu, Lin, Yu et al. 2011; Liu, Lin, Hsiao et al. 2011). "
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