Calpain 2 is required for glioblastoma cell invasion: regulation of matrix metalloproteinase 2.
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.
Jang
Hyo Sang
HS
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
Lal
Sangeet
S
Greenwood
Jeffrey A
JA
D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000494:pharmacology
D034741:RNA, Small Interfering; D002154:Calpain; C569870:CAPN2 protein, human; D020778:Matrix Metalloproteinase 2