Actin cytoskeleton organization, cell surface modification and invasion rate of 5 glioblastoma cell lines differing in PTEN and p53 status

Exp Cell Res. 2015 Jan 15;330(2):346-357. doi: 10.1016/j.yexcr.2014.08.013. Epub 2014 Aug 19.

Abstract

Glioblastoma cells exhibit highly invasive behavior whose mechanisms are not yet fully understood. The present study explores the relationship between the invasion capacity of 5 glioblastoma cell lines differing in p53 and PTEN status, expression of mTOR and several other marker proteins involved in cell invasion, actin cytoskeleton organization and cell morphology. We found that two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) exhibited the highest invasion rates through the Matrigel or collagen matrix. In DK-MG (p53wt/PTENwt) and GaMG (p53mut/PTENwt) cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG (p53wt/PTENmut), U373-MG and SNB19 (both p53mut/PTENmut) cells preferentially expressed F-actin in filopodia and lamellipodia. Scanning electron microscopy confirmed the abundant filopodia and lamellipodia in the PTEN mutated cell lines. Interestingly, the gene profiling analysis revealed two clusters of cell lines, corresponding to the most (U373-MG and SNB19, i.e. p53 and PTEN mutated cells) and less invasive phenotypes. The results of this study might shed new light on the mechanisms of glioblastoma invasion.

Keywords: Actin remodeling; Cell adhesion; Cell matrix; Matrix-metalloprotease; Stress fibers.

MeSH terms

  • Actin Cytoskeleton
  • Actins / biosynthesis
  • Benzothiazoles / pharmacology
  • Brain Neoplasms / pathology*
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Glioblastoma / pathology*
  • Humans
  • MAP Kinase Signaling System / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / biosynthesis
  • Proto-Oncogene Proteins c-akt / biosynthesis
  • RNA Interference
  • RNA, Small Interfering
  • TOR Serine-Threonine Kinases / biosynthesis
  • Toluene / analogs & derivatives
  • Toluene / pharmacology
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Actins
  • Benzothiazoles
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Toluene
  • pifithrin
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human

Associated data

  • GEO/GSE53124