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

Kristin Stock, Jitender Kumar, Michael Synowitz, Stefania Petrosino, Roberta Imperatore, Ewan St J. Smith, Peter Wend, Bettina Purfürst, Ulrike A. Nuber, Ulf Gurok, Vitali Matyash, Joo Hee Wälzlein, Sridhar R. Chirasani, Gunnar Dittmar, Benjamin F. Cravatt, Stefan Momma, Gary R. Lewin, Alessia Ligresti, Luciano De Petrocellis, Luigia CristinoVincenzo Di Marzo, Helmut Kettenmann, Rainer Glass*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

130 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1232-1238
Number of pages7
JournalNature Medicine
Volume18
Issue number8
DOIs
Publication statusPublished - Aug 2012
Externally publishedYes

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