新出版的《自然—醫(yī)學(xué)》Nature Medicine雜志報(bào)道了一種存在于小鼠和人體內(nèi)的抗腫瘤通路,，該通路中包括了一種由神經(jīng)祖細(xì)胞（NPC）分泌出的特殊脂肪酸分子——辣椒素,。
NPC是存在于兒童大腦中的一種細(xì)胞，可用于對(duì)付腫瘤,，能夠分泌物質(zhì)誘導(dǎo)癌細(xì)胞的死亡。
Rainer Glass等人確定這些分泌出的物質(zhì)為辣椒素,，并弄清了辣椒素保護(hù)大腦不受腫瘤侵害的機(jī)制,。辣椒素可通過(guò)辣椒素受體TRPV1發(fā)出信號(hào)，TRPV1在惡性神經(jīng)膠質(zhì)瘤這種大腦癌癥中有著高度表達(dá),，辣椒素發(fā)出信號(hào)后并激活癌細(xì)胞中的一種加強(qiáng)通路促使癌細(xì)胞死亡。
利用一種被稱為arvanil的合成辣椒素對(duì)成年小鼠進(jìn)行腦瘤治療,，便可體現(xiàn)出年輕NPC的這種腫瘤抑制作用,。
該項(xiàng)研究揭示了一種具有潛在強(qiáng)效的利用內(nèi)生腦部分子的腫瘤抑制作用，該抑制作用依賴大量的NPC,，或?qū)Σ煌挲g病人的治療都具有意義,。另外，此次發(fā)現(xiàn)的辣椒素受體TRPV1所傳遞的信號(hào)可作為一種候選通路用于腦瘤的藥物標(biāo)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 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.
