SSEA-3 as a novel amplifying cancer cell surface marker in colorectal cancers
SSEA-3 as a novel amplifying cancer cell surface marker in colorectal cancers
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DOI：
10.3892/ijo.2012.1713
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发表时间：
2013-01-01
影响因子：
5.2
通讯作者：
Yamamoto, Hirofumi
中科院分区：
文献类型：
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作者：
Suzuki, Yozo;Haraguchi, Naotsugu;Yamamoto, Hirofumi
干细胞研究的结果已被应用于癌症干细胞(CSC)的研究，但对ES细胞相关细胞表面标志和CSC之间的关系知之甚少。在这项研究中，我们重点研究了阶段特异性胚胎抗原3(SSEA-3)，它是结直肠癌(CRC)中间充质干细胞和缪斯细胞的标志。研究SSEA-3在人结直肠癌细胞系和临床标本中的表达，特别是SSEA-3表达与CSC标志物(CD44、CD166、ALDH、CD24、CD26)以及与间充质干细胞/缪斯细胞标志物(CD105)的关系。对表达SSEA-3的细胞的成瘤性、球体形成能力、iPS基因(Oct4、NANOG、SOX2和c-Myc)的表达、细胞增殖和细胞周期状态进行检测。Caco-2、DLD-1、HT-29、SW480和HCT116细胞表达SSEA-3，CAR-1细胞不表达SSEA-3。未发现SSEA-3与其他干细胞标记物有显著相关性。与SSEA-3(-)相比，SSEA-3(+)细胞体内致瘤性增强，但体外球体形成能力降低。IPS基因表达与SSEA-3表达状态无关。SSEA-3(+)细胞通过降低p21(Cip1/Waf1)和p27(Kip1)的表达增强细胞周期，从而显示出比SSEA-3(-)更高的增殖能力。临床标本的免疫荧光分析表明，SSEA-3在正常粘膜中仅表达于间质细胞，而在低分化腺癌中广泛表达。提示结直肠癌中SSEA-3(+)细胞具有不成熟的表型，但自我更新能力降低，可能作为肿瘤瞬时扩增细胞或迟发性肿瘤启动细胞发挥作用。
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 p21(Cip1/Waf1) and p27(Kip1). 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.