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Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1

Författare:
  • Kristin Stock
  • Jitender Kumar
  • Michael Synowitz
  • Stefania Petrosino
  • Roberta Imperatore
  • Ewan St J. Smith
  • Peter Wend
  • Bettina Purfuerst
  • Ulrike Nuber
  • Ulf Gurok
  • Vitali Matyash
  • Joo-Hee Waelzlein
  • Sridhar R. Chirasani
  • Gunnar Dittmar
  • Benjamin F. Cravatt
  • Stefan Momma
  • Gary R. Lewin
  • Alessia Ligresti
  • Luciano De Petrocellis
  • Luigia Cristino
  • Vincenzo Di Marzo
  • Helmut Kettenmann
  • Rainer Glass
Publiceringsår: 2012
Språk: Engelska
Sidor: 1232-+
Publikation/Tidskrift/Serie: Nature Medicine
Volym: 18
Nummer: 8
Dokumenttyp: Artikel
Förlag: Nature Publishing Group

Sammanfattning

Primary astrocytomas of grade 3 or 4 according to the classification system of the World Health Organization (high-grade astrocytomas or HGAs) are preponderant among adults and are almost invariably fatal despite the use of multimodal therapy. Here we show that the juvenile brain has an endogenous defense mechanism against HGAs. Neural precursor cells (NPCs) migrate to HGAs, reduce glioma expansion and prolong survival time by releasing endovanilloids that activate the vanilloid receptor (transient receptor potential vanilloid subfamily member-1 or TRPV1) on HGA cells. TRPV1 is highly expressed in tumor and weakly expressed in tumor-free brain. TRPV1 stimulation triggers tumor cell death through the branch of the endoplasmic reticulum stress pathway that is controlled by activating transcription factor-3 (ATF3). The antitumorigenic response of NPCs is lost with aging. NPC-mediated tumor suppression can be mimicked in the adult brain by systemic administration of the synthetic vanilloid arvanil, suggesting that TRPV1 agonists have potential as new HGA therapeutics.

Disputation

Nyckelord

  • Medicine and Health Sciences

Övriga

Published
Yes
  • ISSN: 1078-8956

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