title: Minocycline reduces glioma expansion and invasion by attenuating microglial MT1-MMP expression.
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.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Cellular Neuroscience, Robert Rössle Str. 10, 13125 Berlin, Germany.
authors.forename: D S
authors.initials: DS
authors.lastname: Markovic
authors.forename: K
authors.initials: K
authors.lastname: Vinnakota
authors.forename: N
authors.initials: N
authors.lastname: van Rooijen
authors.forename: J
authors.initials: J
authors.lastname: Kiwit
authors.forename: M
authors.initials: M
authors.lastname: Synowitz
authors.forename: R
authors.initials: R
authors.lastname: Glass
authors.forename: H
authors.initials: H
authors.lastname: Kettenmann
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D002478:Cells, Cultured; D017024:Chemotherapy, Adjuvant; D017077:Culture Media, Conditioned; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008911:Minocycline / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009374:Neoplasms, Experimental; D009924:Organ Culture Techniques
chemical_list: D000903:Antibiotics, Antineoplastic; D017077:Culture Media, Conditioned; D053511:Matrix Metalloproteinase 14; D008911:Minocycline