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

Stock, Kristin; Kumar, Jitender; Synowitz, Michael; Petrosino, Stefania; Imperatore, Roberta; Smith, Ewan St J.; Wend, Peter; Purfuerst, Bettina; Nuber, Ulrike LU and Gurok, Ulf, et al. (2012) In Nature Medicine 18(8). p.1232-1232
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... (More)
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. (Less)
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Nature Medicine
volume
18
issue
8
pages
1232 - 1232
publisher
Nature Publishing Group
external identifiers
  • wos:000307469300029
  • scopus:84864655726
ISSN
1546-170X
DOI
10.1038/nm.2827
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English
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yes
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e2de22ed-c7bd-4c29-8c86-af95d8bad956 (old id 3147250)
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2012-11-01 10:10:30
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2017-11-05 03:55:04
@article{e2de22ed-c7bd-4c29-8c86-af95d8bad956,
  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.},
  author       = {Stock, Kristin and Kumar, Jitender and Synowitz, Michael and Petrosino, Stefania and Imperatore, Roberta and Smith, Ewan St J. and Wend, Peter and Purfuerst, Bettina and Nuber, Ulrike and Gurok, Ulf and Matyash, Vitali and Waelzlein, Joo-Hee and Chirasani, Sridhar R. and Dittmar, Gunnar and Cravatt, Benjamin F. and Momma, Stefan and Lewin, Gary R. and Ligresti, Alessia and De Petrocellis, Luciano and Cristino, Luigia and Di Marzo, Vincenzo and Kettenmann, Helmut and Glass, Rainer},
  issn         = {1546-170X},
  language     = {eng},
  number       = {8},
  pages        = {1232--1232},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1},
  url          = {http://dx.doi.org/10.1038/nm.2827},
  volume       = {18},
  year         = {2012},
}