RUNX3 expression is lost in glioma and its restoration causes drastic suppression of tumor invasion and migration

J Cancer Res Clin Oncol. 2011 Dec;137(12):1823-30. doi: 10.1007/s00432-011-1063-4. Epub 2011 Sep 16.

Abstract

Purpose: The aim of this study is to investigate whether the expression of RUNX3 is related to the development of glioma, and the role of RUNX3 in glioma cells growth, invasion and migration.

Methods: We analyzed the protein expression of RUNX3 by immunohistochemistry in 188 glioma tissues, 8 normal brain tissues and 8 tumor adjacent normal brain tissues using tissue microarray technique. We studied whether RUNX3 restoration can suppress glioma cells growth, invasion and migration by performing MTT cell proliferation assay, matrigel cell invasion assay, wound-healing assay and migration assay. We also detected MMP-2 protein expression and enzyme activity by western blot analysis and gelatin zymography.

Results: We found that RUNX3 expression was decreased in benign tumor and malignant tumor compared with tumor adjacent normal brain tissue (P < 0.01 and P < 0.05, respectively). We did not find any correlation between RUNX3 expression and clinicopathological parameters. In addition, we demonstrated that re-expression of RUNX3 in glioma cells resulted in significantly inhibited cell invasion and migration abilities. This reduced cell invasion and migration abilities were due to MMP-2 protein expression and enzyme activity suppression after RUNX3 restoration.

Conclusions: Our data indicated that RUNX3 expression is significantly decreased in human glioma, and targeting of the RUNX3 pathway may constitute a potential treatment modality for glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / chemistry
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Core Binding Factor Alpha 3 Subunit / analysis
  • Core Binding Factor Alpha 3 Subunit / physiology*
  • Glioma / chemistry
  • Glioma / pathology*
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Neoplasm Invasiveness

Substances

  • Core Binding Factor Alpha 3 Subunit
  • Matrix Metalloproteinase Inhibitors
  • Runx3 protein, human
  • Matrix Metalloproteinase 2