title: Isolation and characterization of cancer stem cells from high-grade serous ovarian carcinomas.
abstract: OBJECTIVE
  In this study, a subpopulation of stem-like cells in human high grade serous ovarian carcinomas (ovarian cancer stem cells; OCSCs) were isolated and characterized.
  
  
  METHODS
  Primary high-grade serous ovarian carcinoma (HGSC) fresh biopsies were cultured under serum-free conditions to produce floating spheres. Sphere formation assay, including self-renewal, differentiation potential, chemo-resistance, and tumorigenicity were determined in vitro or in vivo.
  
  
  RESULTS
  OCSCs overexpressed stem cell genes (Oct-4, Nanog, Sox-2, Bmi-1, Nestin, CD133, CD44, CD24, ALDH1, CD117, and ABCG2). Immunostaining of spheres showed overexpressed Oct-4, Nanog, and Sox-2. These isolated tumor cells expanded as spheroid colonies for more than 30 passages. In contrast, adherent cells expressed high levels of CA125 and CK7. Flow cytometry analysis showed increased CSC markers (CD44, CD24, CD117, CD133, ABCG2, and ALDH1) in the spheroid cell population. OCSCs displayed higher chemoresistance to cisplatin or paclitaxel compared to adherent cells. Moreover, subcutaneous injection of 1 × 104 sphere-forming cells into NOD/SCID mice gave rise to new tumors similar to the original human tumors and could be passaged in mice.
  
  
  CONCLUSIONS
  These results revealed that HGSCs are created and propagated by a small number of undifferentiated tumorigenic cells, and therapeutic targeting of these cells could be beneficial for treatment of HGSCs.
authors: Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
authors: Qi-Zhi
authors: QZ
authors: He
authors: Xun-Zhen
authors: XZ
authors: Luo
authors: Kai
authors: K
authors: Wang
authors: Qian
authors: Q
authors: Zhou
authors: Hong
authors: H
authors: Ao
authors: Yan
authors: Y
authors: Yang
authors: Shu-Xia
authors: SX
authors: Li
authors: Ying
authors: Y
authors: Li
authors: Hui-Ting
authors: HT
authors: Zhu
authors: Tony
authors: T
authors: Duan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000473:pathology; D002448:Cell Adhesion; D000066673:Cell Self Renewal; D002469:Cell Separation / Q000379:methods*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D016513:Mice, SCID; D008875:Middle Aged; D060787:Neoplasm Grading; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor