The p75 neurotrophin receptor is a central regulator of glioma invasion

PLoS Biol. 2007 Aug;5(8):e212. doi: 10.1371/journal.pbio.0050212.


The invasive nature of cancers in general, and malignant gliomas in particular, is a major clinical problem rendering tumors incurable by conventional therapies. Using a novel invasive glioma mouse model established by serial in vivo selection, we identified the p75 neurotrophin receptor (p75(NTR)) as a critical regulator of glioma invasion. Through a series of functional, biochemical, and clinical studies, we found that p75(NTR) dramatically enhanced migration and invasion of genetically distinct glioma and frequently exhibited robust expression in highly invasive glioblastoma patient specimens. Moreover, we found that p75(NTR)-mediated invasion was neurotrophin dependent, resulting in the activation of downstream pathways and producing striking cytoskeletal changes of the invading cells. These results provide the first evidence for p75(NTR) as a major contributor to the highly invasive nature of malignant gliomas and identify a novel therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Cell Line, Tumor
  • Cytoskeleton / metabolism
  • Female
  • Gene Expression Profiling
  • Glioma* / genetics
  • Glioma* / metabolism
  • Glioma* / pathology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Nerve Growth Factors / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Receptor, Nerve Growth Factor / genetics
  • Receptor, Nerve Growth Factor / metabolism*
  • rhoA GTP-Binding Protein / metabolism


  • Nerve Growth Factors
  • Receptor, Nerve Growth Factor
  • Green Fluorescent Proteins
  • rhoA GTP-Binding Protein