Serine protease inhibitor (SERPIN) B1 suppresses cell migration and invasion in glioma cells

Brain Res. 2015 Mar 10:1600:59-69. doi: 10.1016/j.brainres.2014.06.017. Epub 2014 Jun 23.

Abstract

The serine protease inhibitor (SERPIN) B1 is expressed in numerous human tumors, but little is known regarding its role in the pathophysiology of glioma. In this paper, we report that SERPINB1 expression was down-regulated in high-grade human glioma tissue samples and glioblastoma cell lines. To investigate the role of SERPINB1 in glioma migration and invasion, we generated human glioma cell lines in which SERPINB1 was either overexpressed or depleted. Overexpression of SERPINB1 suppressed, while elimination of SERPINB1 promoted, the migration and invasion of glioma cells. SERPINB1 inhibited glioma migration and invasion probably by dampening the expression of matrix metalloproteinase-2 (MMP-2). Molecular data showed that the effect of SERPINB1 in glioma cells might be mediated via sustained inactivation of the phosphorylation of focal adhesion kinase (FAK) involved in the downregulation of the expressions of MMP-2. In a multivariate analysis, high SERPINB1 expression was showed to be associated with good prognosis in glioma. In conclusion, our data suggest that SERPINB1 negatively regulates glioma cell migration and invasion probably by abrogating the expression of MMP-2 and the activation of FAK. We suggest that SERPINB1 may offer the application in clinical medicine.

Keywords: Glioma; Invasion; MMP-2; Migration; SERPINB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Female
  • Focal Adhesion Kinase 1 / metabolism
  • Glioblastoma / metabolism
  • Glioma / metabolism*
  • Glioma / mortality
  • Glioma / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Serpins / metabolism*

Substances

  • Serpins
  • SERPINB1 protein, human
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Matrix Metalloproteinase 2