title: Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.
abstract: Cancer stem-like cells (CSCs)/cancer-initiaiting cells (CICs) are defined as a small population of cancer cells that have self-renewal capacity, differentiation potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have been isolated by side population (SP) analysis, ALDEFLUOR assay and using cell surface markers. However, these approaches are not definitive markers for CSCs/CICs, and it is necessary to refine recent methods for identifying more highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde dehydrogenese bright (ALDH(Br)) cells from ovarian cancer cells. Both SP cells and ALDH(Br) cells exhibited higher tumor-initiating ability and higher expression level of a stem cell marker, sex determining region Y-box 2 (SOX2), than those of main population (MP) cells and ALDH(Low) cells, respectively. We analyzed an SP and ALDH(Br) overlapping population (SP/ALDH(Br)), and the SP/ALDH(Br) population exhibited higher tumor-initiating ability than that of SP cells or ALDH(Br) cells, enabling initiation of tumor with as few as 10(2) cells. Furthermore, SP/ADLH(Br) population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDH(Low), MP/ALDH(Br) and MP/ALDH(Low) cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDH(Br) population was detected in several gynecological cancer cells with ratios of 0.1% for HEC-1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous adenocarcinoma cells. Taken together, use of the SP and ALDH(Br) overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Kazuyo
authors: K
authors: Yasuda
authors: Toshihiko
authors: T
authors: Torigoe
authors: Rena
authors: R
authors: Morita
authors: Takahumi
authors: T
authors: Kuroda
authors: Akari
authors: A
authors: Takahashi
authors: Junichi
authors: J
authors: Matsuzaki
authors: Vitaly
authors: V
authors: Kochin
authors: Hiroko
authors: H
authors: Asanuma
authors: Tadashi
authors: T
authors: Hasegawa
authors: Tsuyoshi
authors: T
authors: Saito
authors: Yoshihiko
authors: Y
authors: Hirohashi
authors: Noriyuki
authors: N
authors: Sato
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D058985:Side-Population Cells / Q000378:metabolism*; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D055748:SOXB1 Transcription Factors; D000444:Aldehyde Dehydrogenase
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