PMID- 21324352 OWN - NLM STAT- MEDLINE DCOM- 20110829 LR - 20220223 IS - 1090-2139 (Electronic) IS - 0889-1591 (Linking) VI - 25 IP - 4 DP - 2011 May TI - Minocycline reduces glioma expansion and invasion by attenuating microglial MT1-MMP expression. PG - 624-8 LID - 10.1016/j.bbi.2011.01.015 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Markovic, D S AU - Markovic DS AD - Max Delbruck Center for Molecular Medicine, Cellular Neuroscience, Robert Rossle Str. 10, 13125 Berlin, Germany. FAU - Vinnakota, K AU - Vinnakota K FAU - van Rooijen, N AU - van Rooijen N FAU - Kiwit, J AU - Kiwit J FAU - Synowitz, M AU - Synowitz M FAU - Glass, R AU - Glass R FAU - Kettenmann, H AU - Kettenmann H LA - eng PT - Journal Article DEP - 20110213 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Culture Media, Conditioned) RN - EC 3.4.24.80 (Matrix Metalloproteinase 14) RN - FYY3R43WGO (Minocycline) SB - IM MH - Animals MH - Antibiotics, Antineoplastic/*pharmacology MH - Brain Neoplasms/*drug therapy/enzymology MH - Cells, Cultured MH - Chemotherapy, Adjuvant MH - Culture Media, Conditioned MH - Glioma/*drug therapy/enzymology MH - Matrix Metalloproteinase 14/*metabolism MH - Mice MH - Microglia/cytology/*drug effects/enzymology MH - Minocycline/*pharmacology MH - Neoplasm Invasiveness/prevention & control MH - Neoplasms, Experimental MH - Organ Culture Techniques EDAT- 2011/02/18 06:00 MHDA- 2011/08/30 06:00 CRDT- 2011/02/18 06:00 PHST- 2010/11/24 00:00 [received] PHST- 2011/01/18 00:00 [revised] PHST- 2011/01/25 00:00 [accepted] PHST- 2011/02/18 06:00 [entrez] PHST- 2011/02/18 06:00 [pubmed] PHST- 2011/08/30 06:00 [medline] AID - S0889-1591(11)00020-1 [pii] AID - 10.1016/j.bbi.2011.01.015 [doi] PST - ppublish SO - Brain Behav Immun. 2011 May;25(4):624-8. doi: 10.1016/j.bbi.2011.01.015. Epub 2011 Feb 13.