Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature medicine, 2012-08, Vol.18 (8), p.1232-1238

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.