title: Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1.
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.
authors: Cellular Neuroscience, Max Delbrück Centre for Molecular Medicine (MDC), Berlin, Germany.
authors: Kristin
authors: K
authors: Stock
authors: Jitender
authors: J
authors: Kumar
authors: Michael
authors: M
authors: Synowitz
authors: Stefania
authors: S
authors: Petrosino
authors: Roberta
authors: R
authors: Imperatore
authors: Ewan St J
authors: ES
authors: Smith
authors: Peter
authors: P
authors: Wend
authors: Bettina
authors: B
authors: Purfürst
authors: Ulrike A
authors: UA
authors: Nuber
authors: Ulf
authors: U
authors: Gurok
authors: Vitali
authors: V
authors: Matyash
authors: Joo-Hee
authors: JH
authors: Wälzlein
authors: Sridhar R
authors: SR
authors: Chirasani
authors: Gunnar
authors: G
authors: Dittmar
authors: Benjamin F
authors: BF
authors: Cravatt
authors: Stefan
authors: S
authors: Momma
authors: Gary R
authors: GR
authors: Lewin
authors: Alessia
authors: A
authors: Ligresti
authors: Luciano
authors: L
authors: De Petrocellis
authors: Luigia
authors: L
authors: Cristino
authors: Vincenzo
authors: V
authors: Di Marzo
authors: Helmut
authors: H
authors: Kettenmann
authors: Rainer
authors: R
authors: Glass
mesh_terms: D000375:Aging / Q000378:metabolism; D000577:Amides; D000581:Amidohydrolases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D002465:Cell Movement; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D009829:Oleic Acids / Q000378:metabolism / Q000494:pharmacology; D010169:Palmitic Acids / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000819:agonists / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D002211:Capsaicin; D017077:Culture Media, Conditioned; D004298:Dopamine; D063388:Endocannabinoids; D004983:Ethanolamines; D009363:Neoplasm Proteins; D009829:Oleic Acids; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C494482:TRPV1 protein, human; C493921:TRPV1 protein, mouse; C474941:arachidonyl dopamine; C121153:arvanil; C488250:oleoylethanolamide; C005958:palmidrol; C078814:anandamide