Atorvastatin suppresses glioma invasion and migration by reducing microglial MT1-MMP expression

J Neuroimmunol. 2013 Jul 15;260(1-2):1-8. doi: 10.1016/j.jneuroim.2013.04.020. Epub 2013 May 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atorvastatin
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 14 / genetics*
  • Matrix Metalloproteinase 14 / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • Neoplasm Invasiveness / pathology
  • Pyrroles / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin
  • p38 Mitogen-Activated Protein Kinases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP14 protein, human
  • Matrix Metalloproteinase 14