Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer
Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer
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DOI：
10.1159/000488743
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Dong, Jiangchuan
中科院分区：
文献类型：
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作者：
Leng, Zhengwei;Xia, Qinghua;Dong, Jiangchuan
背景/目标：虽然EpCAM+ CD 44+细胞比EpCAM-CD 44-细胞表现出更多的干细胞样特性，但EpCAM与CD 44组合在定义CSC中的特异性需要进一步改进。Lgr 5被用作分离结直肠癌中的癌症干细胞（CSC）的生物标志物。然而，Lgr 5与EpCAM和CD 44沿着是否可以进一步鉴定和定义结肠直肠癌中的CSC仍不清楚。研究方法：使用荧光激活细胞分选（FACS）分别分离Lgr 5 + CD 44 + EpCAM+、Lgr 5 + CD 44 + EpCAM-、Lgr 5 + CD 44-EpCAM+、Lgr 5-CD 44 +EpCAM+和Lgr 5-CD 44-EpCAM-细胞。通过体外实验和体内肿瘤异种移植模型研究了这些细胞的集落形成、自我更新、分化和致瘤特性。使用实时PCR检测干细胞基因和CSC和上皮-间质转化（EMT）相关基因的表达，如KLF 4、Oct 4、Sox 2、Nanog、CD 133、CD 44、CD 166、ALDH 1、Lgr 5、E-cadherin、ZO-1、波形蛋白、Snail、Slug和Twist。结果如下：Lgr 5阳性亚群表现出更高的集落形成，自我更新，分化和致瘤性的能力，以及更高的干细胞基因和间充质基因的表达和较低的表达上皮基因比Lgr 5阴性亚群。结论：我们的数据显示，致瘤细胞高度局限于Lgr 5阳性亚群。最重要的是，Lgr 5 + CD 44 +EpCAM+细胞表现出比任何其他亚群更明显的CSC样特征，表明Lgr 5与CD 44和EpCAM组合可以进一步改善结直肠癌中CSC的干细胞样特征。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: Although EpCAM+CD44+ cells exhibit more stem-like properties than did EpCAM-CD44-cells, the specificity of EpCAM combined with CD44 in defining CSCs needs further improvement. Lgr5 is used as a biomarker to isolate cancer stem cells (CSCs) in colorectal cancer. However, it remains unclear whether Lgr5, along with EpCAM and CD44, can further identify and define CSCs in colorectal cancer. Methods: Lgr5+CD44+EpCAM+, Lgr5+CD44+EpCAM-, Lgr5+CD44-EpCAM+, Lgr5-CD44+EpCAM+, and Lgr5-CD44-EpCAM-cells were separately isolated using fluorescence-activated cell sorting (FACS). Colony formation, self-renewal, differentiation, and tumorigenic properties of these cells were investigated through in vitro experiments and in vivo tumor xenograft models. The expression of stemness genes and CSC-and epithelial-mesenchymal transition (EMT)-related genes, such as KLF4, Oct4, Sox2, Nanog, CD133, CD44, CD166, ALDH1, Lgr5, E-cadherin, ZO-1, Vimentin, Snail, Slug, and Twist, was examined using real-time PCR. Results: Lgr5-positive subpopulations exhibited higher capacities for colony formation, self-renewal, differentiation, and tumorigenicity as well as higher expression of stemness genes and mesenchymal genes and lower expression of epithelial genes than did Lgr5-negative subpopulations. Conclusion: Our data revealed that tumorigenic cells were highly restricted to Lgr5-positive subpopulations. Most importantly, Lgr5+CD44+EpCAM+ cells exhibited more pronounced CSC-like traits than did any other subpopulation, indicating that Lgr5 combined with CD44 and EpCAM can further improve the stem-like traits of CSCs in colorectal cancer. (C) 2018 The Author(s) Published by S. Karger AG, Basel