Abstract
Microglia, the immune cells of the brain, often present in large numbers in gliomas, where they promote tumor growth and invasiveness. This study found that atorvastatin reduced the pro-tumorigenic effects of microglia on glioma migration and invasion by reducing the microglial expression of membrane type 1 metalloproteinase (MT1-MMP). The results suggest that down-regulation of MT1-MMP is controlled by a p38 MAPK pathway in microglia. Taken together, the results support further research on atorvastatin as a candidate for glioma therapy by targeting microglia.
Copyright © 2013 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Atorvastatin
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology*
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Cell Line, Tumor
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Cell Movement / drug effects*
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Glioblastoma / genetics
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Glioblastoma / metabolism
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Glioblastoma / pathology*
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Heptanoic Acids / pharmacology*
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
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MAP Kinase Signaling System / drug effects
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Matrix Metalloproteinase 14 / genetics*
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Matrix Metalloproteinase 14 / metabolism
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism
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Microglia / drug effects*
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Microglia / metabolism
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Microglia / pathology
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Neoplasm Invasiveness / pathology
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Pyrroles / pharmacology*
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Heptanoic Acids
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Pyrroles
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Atorvastatin
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p38 Mitogen-Activated Protein Kinases
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MMP2 protein, human
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Matrix Metalloproteinase 2
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MMP14 protein, human
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Matrix Metalloproteinase 14