Ovarian Cancer Stem Cells Are Enriched in Side Population and Aldehyde Dehydrogenase Bright Overlapping Population

Kazuyo Yasuda, Toshihiko Torigoe, Rena Morita, Takahumi Kuroda, Akari Takahashi, Junichi Matsuzaki, Vitaly Kochin, Hiroko Asanuma, Tadashi Hasegawa, Tsuyoshi Saito, Yoshihiko Hirohashi and Noriyuki Sato

PLOS ONE, 2013, vol. 8, issue 8, 1-11

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 (ALDHBr) cells from ovarian cancer cells. Both SP cells and ALDHBr 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 ALDHLow cells, respectively. We analyzed an SP and ALDHBr overlapping population (SP/ALDHBr), and the SP/ALDHBr population exhibited higher tumor-initiating ability than that of SP cells or ALDHBr cells, enabling initiation of tumor with as few as 102 cells. Furthermore, SP/ADLHBr population showed higher sphere-forming ability, cisplatin resistance, adipocyte differentiation ability and expression of SOX2 than those of SP/ALDHLow, MP/ALDHBr and MP/ALDHLow cells. Gene knockdown of SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDHBr 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 ALDHBr overlapping population is a promising approach to isolate highly purified CSCs/CICs and SOX2 might be a novel functional marker for ovarian CSCs/CICs.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0068187

DOI: 10.1371/journal.pone.0068187

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