Helmholtz Gemeinschaft


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

Item Type:Article
Title:Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1
Creators Name:Stock, K. and Kumar, J. and Synowitz, M. and Petrosino, S. and Imperatore, R. and Smith, E.S.J. and Wend, P. and Purfürst, B. and Nuber, U.A. and Gurok, U. and Matyash, V. and Waelzlein, J.H. and Chirasani, S.R. and Dittmar, G. and Cravatt, B.F. and Momma, S. and Lewin, G.R. and Ligresti, A. and De Petrocellis, L. and Cristino, L. and Di Marzo, V. and Kettenmann, H. and Glass, R.
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.
Keywords:Amidohydrolases, Antineoplastic Agents, Apoptosis, Arachidonic Acids, Brain, Brain Neoplasms, Capsaicin, Cell Movement, Conditioned Culture Media, Cultured Tumor Cells, Dopamine, Endocannabinoids, Ethanolamines, Glioblastoma, Neoplasm Proteins, Neoplastic Gene Expression Regulation, Neural Stem Cells, Oleic Acids, Palmitic Acids, Polyunsaturated Alkamides, Real-Time Polymerase Chain Reaction, Small Interfering RNA, TRPV Cation Channels, Animals, Mice
Source:Nature Medicine
Publisher:Nature Publishing Group
Page Range:1232-1238
Date:August 2012
Official Publication:https://doi.org/10.1038/nm.2827
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library