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: Kazuyo Yasuda, Toshihiko Torigoe, Rena Morita, Takahumi Kuroda, Akari Takahashi, Junichi Matsuzaki, Vitaly Kochin, Hiroko Asanuma, Tadashi Hasegawa, Tsuyoshi Saito, Yoshihiko Hirohashi, Noriyuki Sato
• Journal: PloS one (PLoS One) Vol. 8 Issue 8 Pg. e68187 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23967051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SOXB1 Transcription Factors
• Aldehyde Dehydrogenase

Topics

• Aldehyde Dehydrogenase (genetics, metabolism)
• Animals
• Cell Line, Tumor
• Female
• Flow Cytometry
• Heterografts
• Humans
• Mice
• Neoplastic Stem Cells (metabolism)
• Ovarian Neoplasms (genetics, metabolism)
• Phenotype
• SOXB1 Transcription Factors (genetics, metabolism)
• Side-Population Cells (metabolism)
• Spheroids, Cellular
• Tumor Cells, Cultured