期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 46, 期 2, 页码 860-872出版社
KARGER
DOI: 10.1159/000488743
关键词
Lgr5; CD44; EpCAM; Colorectal cancer; Cancer stem cells; Biomarkers; Epithelial-mesenchymal transition
资金
- National Nature Science Foundation of China [81402444, 81402357]
- Key Project of Education Department of Sichuan Province [16ZA0226]
- Chinese Ministry of Science and Technology [14C26213601925]
- Health and Family Planning Commission of Chongqing City [2016MSXM021]
- Project of Science and Technology Department of Sichuan Province [2017JY0170]
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
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