辣椒素或可用于治疗肿瘤

新出版的《自然—医学》Nature Medicine杂志报道了一种存在于小鼠和人体内的抗肿瘤通路，该通路中包括了一种由神经祖细胞（NPC）分泌出的特殊脂肪酸分子——辣椒素。

NPC是存在于儿童大脑中的一种细胞，可用于对付肿瘤，能够分泌物质诱导癌细胞的死亡。

Rainer Glass等人确定这些分泌出的物质为辣椒素，并弄清了辣椒素保护大脑不受肿瘤侵害的机制。辣椒素可通过辣椒素受体TRPV1发出信号，TRPV1在恶性神经胶质瘤这种大脑癌症中有着高度表达，辣椒素发出信号后并激活癌细胞中的一种加强通路促使癌细胞死亡。

利用一种被称为arvanil的合成辣椒素对成年小鼠进行脑瘤治疗，便可体现出年轻NPC的这种肿瘤抑制作用。

该项研究揭示了一种具有潜在强效的利用内生脑部分子的肿瘤抑制作用，该抑制作用依赖大量的NPC，或对不同年龄病人的治疗都具有意义。另外，此次发现的辣椒素受体TRPV1所传递的信号可作为一种候选通路用于脑瘤的药物标靶。（生物谷Bioon.com）


doi:10.1038/nm.2827
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Neural precursor cells induce cell death of high-grade astrocytomas through stimulation of TRPV1

Kristin Stock,1, 16 Jitender Kumar,1, 16 Michael Synowitz,1, 2, 16 Stefania Petrosino,3 Roberta Imperatore,4 Ewan St J Smith,5, 6 Peter Wend,7, 15 Bettina Purfürst,8 Ulrike A Nuber,9 Ulf Gurok,10 Vitali Matyash,1 Joo-Hee Wälzlein,1 Sridhar R Chirasani,1 Gunnar Dittmar,11 Benjamin F Cravatt,12 Stefan Momma,13 Gary R Lewin,5 Alessia Ligresti,3 Luciano De Petrocellis,4 Luigia Cristino,4 Vincenzo Di Marzo,3 Helmut Kettenmann1, 16 & Rainer Glass1, 14, 16


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 transc[x]ription 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.