Endogenous tenascin-C enhances glioblastoma invasion with reactive change of surrounding brain tissue

Cancer Sci. 2009 Aug;100(8):1451-9. doi: 10.1111/j.1349-7006.2009.01189.x. Epub 2009 Apr 20.

Abstract

Tenascin-C is an extracellular matrix glycoprotein implicated in embryogenesis, wound healing and tumor progression. We previously revealed that tenascin-C expression is correlated with the prognosis of patients with glioblastoma. However, the exact role of endogenous tenascin-C in regulation of glioblastoma proliferation and invasion remains to be established. We show here that endogenous tenascin-C facilitates glioblastoma invasion, followed by reactive change of the surrounding brain tissue. Although shRNA-mediated knockdown of endogenous tenascin-C does not affect proliferation of glioblastoma cells, it abolishes cell migration on a two-dimensional substrate and tumor invasion with brain tissue changes in a xenograft model. The tyrosine phosphorylation of focal adhesion kinase, a cytoplasmic tyrosine kinase that associates with integrins, was decreased in tenascin-C-knockdown cells. In the analysis of clinical samples, tenascin-C expression correlates with the volume of peritumoral reactive change detected by magnetic resonance imaging. Interestingly, glioblastoma cells with high tenascin-C expression infiltrate brain tissue in an autocrine manner. Our results suggest that endogenous tenascin-C contributes the invasive nature of glioblastoma and the compositional change of brain tissue, which renders tenascin-C as a prime candidate for anti-invasion therapy for glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / physiopathology
  • Cell Line, Tumor
  • Cell Movement
  • Fluocinolone Acetonide / metabolism
  • Genetic Vectors
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology*
  • Glioblastoma / physiopathology
  • Glioblastoma / surgery
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Lentivirus / genetics
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Radiography
  • Tenascin / metabolism*
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Ki-67 Antigen
  • RNA, Small Interfering
  • Tenascin
  • enhanced green fluorescent protein
  • Fluocinolone Acetonide
  • Green Fluorescent Proteins