Integrin α3 is overexpressed in glioma stem-like cells and promotes invasion

Br J Cancer. 2013 Jun 25;108(12):2516-24. doi: 10.1038/bjc.2013.218. Epub 2013 May 7.


Background: Glioma stem-like cell (GSC) properties are responsible for gliomagenesis and recurrence. GSCs are invasive but its mechanism remains to be elucidated. Here, we attempted to identify the molecules that promote invasion in GSCs.

Methods: Neurospheres and CD133⁺ cells were collected from glioblastoma (GBM) specimens and glioma cell lines by sphere-formation method and magnetic affinity cell sorting, respectively. Differential expression of gene candidates, its role in invasion and its signaling pathway were evaluated in glioma cell lines.

Results: Neurospheres from surgical specimens attached to fibronectin and laminin, the receptors of which belong to the integrin family. Integrin α3 was overexpressed in CD133⁺ cells compared with CD133⁻ cells in all the glioma cell lines (4 out of 4). Immunohistochemistry demonstrated the localisation of integrin α3 in GBM cells, including invading cells, and in the tumour cells around the vessels, which is believed to be a stem cell niche. The expression of integrin α3 was correlated with migration and invasion. The invasion activity of glioma cells was linked to the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2.

Conclusion: Our results suggest that integrin α3 contributes to the invasive nature of GSCs via ERK1/2, which renders integrin α3 a prime candidate for anti-invasion therapy for GBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibronectins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Integrin alpha3 / genetics*
  • Integrin alpha3 / metabolism
  • Integrin alpha3 / physiology*
  • MAP Kinase Signaling System / physiology
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Phosphorylation
  • Tumor Cells, Cultured
  • Up-Regulation / genetics


  • FN1 protein, human
  • Fibronectins
  • Integrin alpha3
  • Extracellular Signal-Regulated MAP Kinases