Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1
Primary astrocytomas of World Health Organization grade 3 and grade 4 (HG-astrocytomas) are preponderant among adults and are almost invariably fatal despite multimodal therapy. Here, we show that the juvenile brain has an endogenous defense mechanism against HG-astrocytomas. Neural precursor cells...
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2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480991/ |
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pubmed-34809912013-07-26 Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1 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 Article Primary astrocytomas of World Health Organization grade 3 and grade 4 (HG-astrocytomas) are preponderant among adults and are almost invariably fatal despite multimodal therapy. Here, we show that the juvenile brain has an endogenous defense mechanism against HG-astrocytomas. Neural precursor cells (NPCs) migrate to HG-astrocytomas, reduce glioma expansion and prolong survival by releasing a group of fatty acid ethanolamides that have agonistic activity on the vanilloid receptor (transient receptor potential vanilloid subfamily member-1; TRPV1). TRPV1 expression is higher in HG-astrocytomas than in tumor-free brain and TRPV1 stimulation triggers tumor cell death via the activating transcription factor-3 (ATF3) controlled branch of the ER stress pathway. The anti-tumorigenic 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 hold potential as new HG-astrocytoma therapeutics. 2012-07-22 2012-08 /pmc/articles/PMC3480991/ /pubmed/22820645 http://dx.doi.org/10.1038/nm.2827 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
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Open Access Journal |
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Foreign Institution |
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US National Center for Biotechnology Information |
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NCBI PubMed |
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Online Access |
| language |
English |
| format |
Online |
| author |
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 |
| spellingShingle |
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 Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1 |
| author_facet |
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 |
| author_sort |
Stock, Kristin |
| title |
Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1 |
| title_short |
Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1 |
| title_full |
Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1 |
| title_fullStr |
Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1 |
| title_full_unstemmed |
Neural precursor cells induce cell death of high-grade astrocytomas via stimulation of TRPV1 |
| title_sort |
neural precursor cells induce cell death of high-grade astrocytomas via stimulation of trpv1 |
| description |
Primary astrocytomas of World Health Organization grade 3 and grade 4 (HG-astrocytomas) are preponderant among adults and are almost invariably fatal despite multimodal therapy. Here, we show that the juvenile brain has an endogenous defense mechanism against HG-astrocytomas. Neural precursor cells (NPCs) migrate to HG-astrocytomas, reduce glioma expansion and prolong survival by releasing a group of fatty acid ethanolamides that have agonistic activity on the vanilloid receptor (transient receptor potential vanilloid subfamily member-1; TRPV1). TRPV1 expression is higher in HG-astrocytomas than in tumor-free brain and TRPV1 stimulation triggers tumor cell death via the activating transcription factor-3 (ATF3) controlled branch of the ER stress pathway. The anti-tumorigenic 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 hold potential as new HG-astrocytoma therapeutics. |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480991/ |
| _version_ |
1611918853876482048 |