Enrichment and characterization of ovarian cancer stem cells and its potential clinical application

Wenxia Wang, Zhenbo Zhang, Yin Zhao, Zeng Yuan, Xingsheng Yang, Beihua Kong, Wenxin Zheng

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The cancer stem cell (CSC) theory proposes that a minor population in tumor cells with specific features, such as self-renewal and reproducible tumor phenotype could contribute to tumor relapse and chemotherapy resistance. Several studies have convincingly documented the existence of ovarian CSC, but questions related to the biologic behavior and specific biomarkers of ovarian CSC remain to be clarified. In the present study, we firstly established a tumor cell line with capability of regenerating tumors through serial transplantation of ovarian tumor tissue in non-obese/severe combined immunodeficient (SCID) mice. After separation of CD133+ cells with magnetic beads, we compared the phenotype and biologic behavior of CD133+ versus CD133- cells. It was found that the CD133+ cells were much more potent to produce colonies in semi-solid agar culture than CD133- cells. The proportion of the cells in G0/1 cell cycle is much higher in CD133+ cells than in CD133- cells. Furthermore, in vivo experiments demonstrated that the CD133+ cells were capable of repeatedly regenerate tumors in NOD/SCID mice, while the CD133- cells were not. Compared with CD133- cells, the CD133+ cells expressed much higher levels of the stem cell markers Oct4, Sox2, Nanog and Mcl-1. Clinically, among a total of 290 ovarian epithelial cancers, increased level of CD133 expression was positively correlated with a high cancer stage and had a worse 5-year survival rate. Taken together, the results suggest that the CD133+ cells from human ovarian cancer have the characteristics of CSC, which may contribute to ovarian cancer relapse and anti-apoptotic activity. The method of ovarian CSC enrichment we established provides a feasible and practical way of ovarian cancer research in a molecular level. In addition, CD133 may be used as a prognostic marker for ovarian epithelial cancer, which may have a role for future therapeutic effect.

Original languageEnglish (US)
Pages (from-to)10128-10138
Number of pages11
JournalInternational Journal of Clinical and Experimental Pathology
Volume9
Issue number10
StatePublished - Jan 1 2016

Keywords

  • CD133
  • Cancer stem cells
  • Ovarian epithelial cancer

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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