Cervical cancer cells with positive Sox2 expression exhibit the properties of cancer stem cells.
Cervical cancer cells with positive Sox2 expression exhibit the properties of cancer stem cells.
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DOI：
10.1371/journal.pone.0087092
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zheng PS
中科院分区：
文献类型：
--
作者：
Liu XF;Yang WT;Xu R;Liu JT;Zheng PS
尽管Sox 2表达已在几种类型的癌症中发现，但其尚未用于鉴定或分离体细胞癌中的CSC。用含有驱动增强型绿色荧光蛋白（EGFP）报告基因的人Sox 2转录元件的质粒稳定转染SiHa和C33 A细胞，通过FACS分选成Sox 2阳性和Sox 2阴性群体，并通过western blot和免疫组织化学检测Sox 2表达。在体外和体内研究了Sox 2阳性和Sox 2阴性宫颈癌细胞的分化、自我更新和成瘤能力，以及干细胞和EMT相关基因的表达。利用pSox 2/EGFP系统从宫颈癌细胞系SiHa和C33 A中分离Sox 2阳性和Sox 2阴性细胞。与Sox 2阴性细胞相比，Sox 2阳性的SiHa和C33 A细胞表现出更强的自我更新、分化和成瘤能力。此外，Sox 2阳性的SiHa和C33 A细胞表达更高水平的干细胞相关基因，如Sox 2/Bmi-1/Oct 4/ALDH 1，和EMT相关基因，如波形蛋白/蜗牛/β-连环蛋白。综上所述，所有这些结果表明，表达内源性Sox 2的细胞是宫颈癌中的CSC。这项研究是第一个建立宫颈癌中内源性Sox 2表达和CSC之间的功能联系。此外，这项研究表明，开发一种基于内源性核蛋白Sox 2而不是细胞表面标志物的表达从体细胞肿瘤中分离CSC的工具是可行的。
Although Sox2 expression has been found in several types of cancer, it has not yet been used to identify or isolate CSCs in somatic carcinoma. SiHa and C33A cells stably transfected with a plasmid containing human Sox2 transcriptional elements driving the enhanced green fluorescent protein (EGFP) reporter were sorted into the Sox2-positive and the Sox2-negative populations by FACS, and Sox2 expression was detected by western blot and immunohistochemistry. The differentiation, self-renewal and tumor formation abilities, as well as the expression of the stemness and the EMT related genes of the Sox2-positive and the Sox2-negative cervical cancer cells were characterized in vitro and in vivo. A pSox2/EGFP system was used to separate the Sox2-positive and the Sox2-negative cells from cervical cancer cell lines, SiHa and C33A cells. Compared with the Sox2-negative cells, the Sox2-positive SiHa and C33A cells exhibited greater capacities for self-renewal, differentiation and tumor formation. Furthermore, Sox2-positive SiHa and C33A cells expressed higher levels of stemness-related genes, such as Sox2/Bmi-1/Oct4/ALDH1, and EMT-related genes, such as vimentin/snail/β-catenin. Taken together, all these results indicated that cells expressing endogenous Sox2 are CSCs in cervical carcinomas. This study is the first to establish a functional link between endogenous Sox2 expression and CSCs in cervical carcinomas. Additionally, this study demonstrated that it is feasible to develop a tool to isolate CSCs from somatic tumors based on the expression of the endogenous nuclear protein Sox2 instead of cell surface markers.
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影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
影响因子：
3.8
作者：
López J;Poitevin A;Mendoza-Martínez V;Pérez-Plasencia C;García-Carrancá A
通讯作者：
García-Carrancá A
影响因子：
2.7
作者：
Bani-Yaghoub, Mahmud;Tremblay, Roger G.;Sikorska, Marianna
通讯作者：
Sikorska, Marianna
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
50.3
作者：
O'Brien, Catherine A.;Kreso, Antonija;Dick, John E.
通讯作者：
Dick, John E.