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

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsXiao-Fang Liu, Wen-Ting Yang, Rui Xu, Jun-Tian Liu, Peng-Sheng Zheng
JournalPloS one (PLoS One) Vol. 9 Issue 1 Pg. e87092 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID24489842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Nuclear Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
Topics
  • Biomarkers, Tumor (metabolism)
  • Carcinogenesis (metabolism, pathology)
  • Cell Differentiation (genetics)
  • Cell Line, Tumor
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition (genetics)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Green Fluorescent Proteins (metabolism)
  • Humans
  • Neoplastic Stem Cells (metabolism, pathology)
  • Nuclear Proteins (metabolism)
  • Plasmids (metabolism)
  • SOXB1 Transcription Factors (genetics, metabolism)
  • Transcription, Genetic
  • Transplantation, Heterologous
  • Uterine Cervical Neoplasms (genetics, metabolism, pathology)

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