Calpain 2 is required for glioblastoma cell invasion: Regulation of matrix metalloproteinase 2

Hyo Sang Jang, Sangeet Lal, Jeffrey A. Greenwood

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Invasion of glioblastoma cells significantly reduces the effectiveness of current treatments, highlighting the importance of understanding dispersal mechanisms and characteristics of the invasive population. Induction of calcium fluxes into glioblastoma cells by autocrine glutamate is critical for invasion. However, the target(s) by which calcium acts to stimulate the dispersal of glioblastoma cells is not clear. In this study, we tested the hypothesis that the calcium-activated protease calpain 2 is required for glioblastoma cell invasion. Knockdown of calpain 2 expression using shRNA or chemical inhibition of calpain activity reduced glioblastoma cell invasion by 90%. Interestingly, decreased expression of calpain 2 did not influence morphology or migration, suggesting regulation of invasion specific mechanisms. Consistent with this idea, 39% less extracellular MMP2 was measured from knockdown cells identifying one mechanism by which calpain 2 mediates glioblastoma cell invasion. This is the first report demonstrating that calpain 2 is required for glioblastoma cell invasion.

Original languageEnglish (US)
Pages (from-to)1796-1804
Number of pages9
JournalNeurochemical Research
Volume35
Issue number11
DOIs
StatePublished - Nov 2010
Externally publishedYes

Keywords

  • Calcium
  • Calpain
  • Glioblastoma
  • Glutamate
  • Invasion
  • Matrix metalloproteinase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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