研究發(fā)現(xiàn)AQP5揭示了胃干細(xì)胞和胃癌起源
2020-02-10
來(lái)源：小柯機(jī)器人
新加坡科技研究局Nick Barker研究組的研究發(fā)現(xiàn)AQP5豐富了對(duì)遠(yuǎn)端胃中的干細(xì)胞和胃癌起源的認(rèn)知。2020年2月5日，國(guó)際學(xué)術(shù)期刊《自然》在線發(fā)表了這一成果。
研究人員通過沿小鼠胃腸道LGR5 +干細(xì)胞群體的比較分析鑒定，并在功能上驗(yàn)證膜蛋白AQP5可作為小鼠和人類成年幽門干細(xì)胞的標(biāo)志物。研究人員利用新生的Aqp5-creERT2小鼠模型發(fā)現(xiàn)，AQP5 +隔室內(nèi)的干細(xì)胞是WNT驅(qū)動(dòng)的體內(nèi)侵入性胃癌細(xì)胞的來(lái)源。此外，腫瘤駐留的AQP5 +細(xì)胞可以在體外選擇性啟動(dòng)類器官生長(zhǎng)，這表明該種細(xì)胞包含潛在的癌癥干細(xì)胞。在人類中，AQP5主要在腸道和彌漫性亞型的胃癌中（以及在這些亞型的轉(zhuǎn)移中）表達(dá)，并且與健康組織相比，常表現(xiàn)出細(xì)胞定位的改變。這些新近鑒定出的標(biāo)記物和小鼠模型將為破譯胃癌早期形成以及人胃干細(xì)胞的分離和表征提供寶貴資源，這也為臨床上利用這些細(xì)胞進(jìn)行再生醫(yī)學(xué)提供了可能。
據(jù)介紹，LGR5標(biāo)記了小鼠幽門胃腺體基部的成年上皮干細(xì)胞，但是由于缺乏可用于其分離和驗(yàn)證的表面標(biāo)記物，因此其等效的人類干細(xì)胞群體仍然未知。在腸道癌的小鼠模型中，WNT途徑過度激活后，LGR5 +腸道干細(xì)胞是癌癥細(xì)胞的主要來(lái)源。然而，WNT信號(hào)通路失調(diào)后幽門LGR5 +干細(xì)胞對(duì)胃癌進(jìn)展的作用是未知的（這是人類胃癌中的常見事件）。
附：英文原文
Title: AQP5 enriches for stem cells and cancer origins in the distal stomach
Author: Si Hui Tan, Yada Swathi, Shawna Tan, Jasmine Goh, Ryo Seishima, Kazuhiro Murakami, Masanobu Oshima, Toshikatsu Tsuji, Phyllis Phuah, Liang Thing Tan, Esther Wong, Aliya Fatehullah, Taotao Sheng, Shamaine Wei Ting Ho, Heike I. Grabsch, Supriya Srivastava, Ming Teh, Simon L. I. J. Denil, Seri Mustafah, Patrick Tan, Asim Shabbir, Jimmy So, Khay Guan Yeoh, Nick Barker
Issue&Volume: 2020-02-05
Abstract:LGR5 marks resident adult epithelial stem cells at the gland base in the mouse pyloric stomach1, but the identity of the equivalent human stem cell population remains unknown owing to a lack of surface markers that facilitate its prospective isolation and validation. In mouse models of intestinal cancer, LGR5+ intestinal stem cells are major sources of cancer following hyperactivation of the WNT pathway2. However, the contribution of pyloric LGR5+ stem cells to gastric cancer following dysregulation of the WNT pathway—a frequent event in gastric cancer in humans3—is unknown. Here we use comparative profiling of LGR5+ stem cell populations along the mouse gastrointestinal tract to identify, and then functionally validate, the membrane protein AQP5 as a marker that enriches for mouse and human adult pyloric stem cells. We show that stem cells within the AQP5+ compartment are a source of WNT-driven, invasive gastric cancer in vivo, using newly generated Aqp5-creERT2 mouse models. Additionally, tumour-resident AQP5+ cells can selectively initiate organoid growth in vitro, which indicates that this population contains potential cancer stem cells. In humans, AQP5 is frequently expressed in primary intestinal and diffuse subtypes of gastric cancer (and in metastases of these subtypes), and often displays altered cellular localization compared with healthy tissue. These newly identified markers and mouse models will be an invaluable resource for deciphering the early formation of gastric cancer, and for isolating and characterizing human-stomach stem cells as a prerequisite for harnessing the regenerative-medicine potential of these cells in the clinic.
DOI: 10.1038/s41586-020-1973-x
Source: https://www.nature.com/articles/s41586-020-1973-x
聲明：本文版權(quán)歸原作者所有，轉(zhuǎn)載文章僅為傳播更多信息，如作者信息標(biāo)記有誤，或侵犯您的版權(quán)，請(qǐng)聯(lián)系我們，我們將在及時(shí)修改或刪除內(nèi)容，聯(lián)系郵箱：marketing@360worldcare.com
