Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1.
Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1.
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DOI：
10.1038/nm.2827
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发表时间：
2012-08
期刊：
影响因子：
82.9
通讯作者：
Glass, Rainer
中科院分区：
文献类型：
--
作者：
Stock, Kristin;Kumar, Jitender;Synowitz, Michael;Petrosino, Stefania;Imperatore, Roberta;Smith, Ewan St J.;Wend, Peter;Purfuerst, Bettina;Nuber, Ulrike A.;Gurok, Ulf;Matyash, Vitali;Waelzlein, 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
世界卫生组织3级和4级原发性星形细胞瘤（hg -星形细胞瘤）在成人中占多数，尽管采用多种治疗方法，但几乎总是致命的。在这里，我们发现青少年大脑具有内源性防御hg星形细胞瘤的机制。神经前体细胞（Neural precursor cells, npc）通过释放一组对香草样蛋白受体（瞬时受体潜在香草样蛋白亚家族成员-1；TRPV1）具有激动作用的脂肪酸乙醇酰胺，向pg -星形细胞瘤迁移，减少胶质瘤的扩张，延长生存期。TRPV1在g -星形细胞瘤中的表达高于无瘤脑，TRPV1刺激通过内质网应激途径的激活转录因子-3 （ATF3）控制分支触发肿瘤细胞死亡。npc的抗肿瘤反应随着年龄的增长而消失。npc介导的肿瘤抑制可以通过全身给药合成香草素Arvanil在成人大脑中模拟，这表明TRPV1激动剂具有作为新的hg星形细胞瘤治疗药物的潜力。
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.
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影响因子：
14.5
作者：
Chirasani, Sridhar Reddy;Sternjak, Alexander;Glass, Rainer
通讯作者：
Glass, Rainer
影响因子：
14.9
作者：
Grünweller, A;Wyszko, E;Kurreck, J
通讯作者：
Kurreck, J
DOI：
10.1073/pnas.0708228104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Leuner, Benedetta;Kozorovitskiy, Yevgenia;Gould, Elizabeth
通讯作者：
Gould, Elizabeth
影响因子：
5.3
作者：
Assanah, Marcela;Lochhead, Richard;Canoll, Peter
通讯作者：
Canoll, Peter
影响因子：
4.8
作者：
Bisogno, T;Maurelli, S;DiMarzo, V
通讯作者：
DiMarzo, V