The p75 neurotrophin receptor is a central regulator of glioma invasion

Angela L.M. Johnston, Xueqing Lun, Jennifer J. Rahn, Abdelhamid Liacini, Limei Wang, Mark G. Hamilton, Ian F. Parney, Barbara L. Hempstead, Stephen M. Robbins, Peter A. Forsyth, Donna L. Senger

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

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 p75NTR dramatically enhanced migration and invasion of genetically distinct glioma and frequently exhibited robust expression in highly invasive glioblastoma patient specimens. Moreover, we found that p75NTR-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 p75NTR as a major contributor to the highly invasive nature of malignant gliomas and identify a novel therapeutic target.

Original languageEnglish (US)
Pages (from-to)1723-1737
Number of pages15
JournalPLoS biology
Volume5
Issue number8
DOIs
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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