Cervical cancer cells with positive Sox2 expression exhibit the properties of cancer stem cells.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Reproductive Medicine, the First Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China ; Department of Pharmacology, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China.
Xiao-Fang
XF
Liu
Department of Reproductive Medicine, the First Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China ; Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China.
Wen-Ting
WT
Yang
Department of Reproductive Medicine, the First Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China.
Rui
R
Xu
Department of Pharmacology, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China.
Jun-Tian
JT
Liu
Department of Reproductive Medicine, the First Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China ; Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China ; Division of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University Medical School, Xi'an, The People's Republic of China.
Peng-Sheng
PS
Zheng
D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins