Metastasis tumor-associated protein-2 knockdown suppresses the proliferation and invasion of human glioma cells in vitro and in vivo

J Neurooncol. 2014 Nov;120(2):273-81. doi: 10.1007/s11060-014-1558-3. Epub 2014 Jul 22.

Abstract

Metastasis tumor-associated protein 2 (MTA2) is a member of the MTA family that is closely associated with tumor progression and metastasis. However, the role of MTA2 in glioma cells remains unclear. The expression of MTA2 was measured using immunohistochemistry and western blotting in the human brain tumor tissue array and human glioma cell lines. The impact of MTA2 knockdown on GBM8401 and Hs683 cell growth was evaluated by MTT assay and flow cytometry. Cell migration and invasion were analyzed by cell-migration assay and Matrigel invasion assay. In addition, we used subcutaneous tumor models to study the effect of MTA2 on the growth of glioma cells in vivo. We found that MTA2 protein and mRNA expression are higher in GBM8401 and Hs683 cells than in other glioma cells (M059 J, M059 K and U-87 MG), and glioma tumor tissue correlated significantly with tumor grade (P < 0.001). Knockdown of MTA2 expression significantly inhibited cell growth, cell migration and invasion, and induced G0/G1 phase arrest in human GBM8401 and Hs683 cells in vitro. Moreover, in vivo studies using subcutaneous xenografts in mice models indicate that MTA2 knockdown significantly inhibited tumorigenicity. These results indicate that MTA2 plays an important oncogenic role in the development and progression of gliomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Brain / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Case-Control Studies
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Flow Cytometry
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Grading
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Messenger
  • RNA, Small Interfering
  • Repressor Proteins
  • MTA2 protein, human
  • Histone Deacetylases