title: Observation of ovarian cancer stem cell behavior and investigation of potential mechanisms of drug resistance in three-dimensional cell culture.
abstract: Cancer cells behave differently in a three-dimensional (3D) cell culture compared with in the conventional two-dimensional (2D) one. Accumulated evidences indicate that the characteristics of cancer stem cells (CSCs) are different from common cancer cells due to their ability to produce tumors and resist chemoradiation. The objective of this work was to observe CSC behavior and investigate the potential mechanisms of CSC drug resistance in 3D versus 2D in vitro environment. We first demonstrated that the CD44(+)CD117(+)cells isolated from the human epithelial ovarian cancer HO8910 cell line have the properties of CSCs that revealed faster growth, larger tumorsphere and stronger survival potential in the hypoxic environment in 3D cell culture as well as more powerful tumorigenicity in a xenograft mice than the HO8910 cells. The CD44(+)CD117(+)CSCs also exhibited high chemoresistance to anticancer drugs when the cells were incubated with 5-fluorouracil, cisplatin and carboplatin, respectively in 3D versus 2D environment. This might be associated with the high expression of ABCG2, ABCB1 and the high expression of MMP-2 and MMP-9 in CD44(+)CD117(+)CSCs. Overall, these results suggest the advantages of using 3D culture model to accurately display CSC behavior in vitro. 3D model may improve the efficacy of screening anticancer drugs for treatment of ovarian CSCs.
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China.
authors.forename: Junsong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gynecology and Obstetrics, Zhongda Hospital, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China; Department of Gynecology and Obstetrics, Zhongda Hospital, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China.
authors.forename: Dengyu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Kai
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China; Department of Oncology, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School, Southeast University, Dingjiaqiao 87, Nanjing 210009, China. Electronic address: njdoujun@sina.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D016190:Carboplatin / Q000494:pharmacology; D063646:Carcinogenesis / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil
keywords: Cancer stem cells; Chemoresistance; Epithelial ovarian cancer; Three-dimensional culture; Two-dimensional culture