SSEA-3 as a novel amplifying cancer cell surface marker in colorectal cancers

Suzuki,Yozo; Haraguchi,Naotsugu; Takahashi,Hidekazu; Uemura,Mamoru; Nishimura,Junichi; Hata,Taishi; Takemasa,Ichiro; Mizushima,Tsunekazu; Ishii,Hideshi; Doki,Yuichiro; Mori,Masaki; Yamamoto,Hirofumi

doi:10.3892/ijo.2012.1713

SSEA-3 as a novel amplifying cancer cell surface marker in colorectal cancers

Authors:
- Yozo Suzuki
- Naotsugu Haraguchi
- Hidekazu Takahashi
- Mamoru Uemura
- Junichi Nishimura
- Taishi Hata
- Ichiro Takemasa
- Tsunekazu Mizushima
- Hideshi Ishii
- Yuichiro Doki
- Masaki Mori
- Hirofumi Yamamoto
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Affiliations: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan, Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
Published online on: November 22, 2012 https://doi.org/10.3892/ijo.2012.1713
Pages: 161-167

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Abstract

Findings from studies on stem cells have been applied to cancer stem cell (CSC) research, but little is known about the relationship between ES cell-related cell surface markers and CSCs. In this study, we focused on stage-specific embryonic antigen 3 (SSEA-3), a marker of mesenchymal stem cells and Muse cells in colorectal cancer (CRC). Expression of SSEA-3 in human CRC cell lines and clinical specimens, specifically the relationship of SSEA-3 expression and the representative CSC markers (CD44, CD166, ALDH, CD24 and CD26) as well as with mesenchymal stem cell/Muse cell marker (CD105) were assessed. To characterize SSEA-3-expressing cells, tumorigenicity, sphere formation ability, expression of iPS genes (Oct4, NANOG, SOX2 and c-Myc), cell proliferation and cell cycle status were assessed. SSEA-3 expression was identified in Caco-2, DLD-1, HT-29, SW480 and HCT116, but not in CaR-1 cells. No significant relationship between SSEA-3 and other stem cell markers was detected. SSEA-3+ cells showed increased tumorigenicity in vivo, but lower sphere formation ability in vitro than SSEA-3-. iPS gene expression was not correlated with SSEA-3 expression status. SSEA-3+ cells showed higher proliferative ability than SSEA-3- through enhanced cell cycles by decreased expression of p21Cip1/Waf1 and p27Kip1. Immunofluorescence analysis in clinical specimens indicated that expression of SSEA-3 is limited to stromal cells in normal mucosa but broad in poorly differentiated adenocarcinoma. These observations indicated that SSEA-3+ cells in CRC have immature phenotype but decreased self-renewal ability and may function as tumor transient amplifying cells or delayed contributing tumor-initiating cells.

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