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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-08

AUTHORS

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 Cristino, Vincenzo Di Marzo, Helmut Kettenmann, Rainer Glass

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. More... »

PAGES

1232

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.2827

DOI

http://dx.doi.org/10.1038/nm.2827

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023224788

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22820645


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