Isolation and characterization of tumorigenic extrahepatic cholangiocarcinoma cells with stem cell‐like properties
Isolation and characterization of tumorigenic extrahepatic cholangiocarcinoma cells with stem cell‐like properties
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DOI：
10.1002/ijc.25317
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发表时间：
2011
影响因子：
6.4
通讯作者：
Min Wang;Juan Xiao;Min Shen;Yahong Yu;Rui Tian;F. Zhu;Jianxin Jiang;Zhi-yong Du;Jun X Hu;Wen-song Liu;R. Qin
中科院分区：
文献类型：
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作者：
Min Wang;Juan Xiao;Min Shen;Yahong Yu;Rui Tian;F. Zhu;Jianxin Jiang;Zhi-yong Du;Jun X Hu;Wen-song Liu;R. Qin
最近的研究表明，形成和生长肿瘤的能力特异性地存在于称为癌症干细胞（CSC）的小细胞群中。这些研究主要针对各种人类癌症进行;然而，尚未尝试从胆管癌中分离和表征干细胞。分子标志物CD 24、CD 44、CD 34和上皮细胞粘附分子（EpCAM）被广泛地单独或组合用于表征某些类型的CSC。在这项研究中，我们使用这些标志物来鉴定肝外胆管癌（ECC）中具有癌症干/祖细胞样特性的细胞亚群。我们发现在人ECC组织中存在CD 24 + CD 44 + EpCAM高细胞（0.39-2.27%）。CD 24 + CD 44 + EpCAM高亚群的表达与原发性癌症一致，并且可以在NOD/SCID小鼠的连续体内传代期间复制。与CD 24 − CD 44 − EpCAM low/−细胞相比，从3例胆管癌异种移植物中分离的CD 24 + CD 44 + EpCAM high细胞显示出较高的致瘤潜力。这些致瘤ECC细胞表现出自我更新的干细胞特性和产生异质后代的能力。我们报告了一个CSC人口的ECC的特点是CD 24，CD 44和EpCAM表型的鉴定。我们的发现可以为胆管癌的肿瘤发生提供新的见解，并为抗癌治疗提供潜在的靶点。
Recent studies suggest that the ability to form and grow tumors specifically resides in a small cell population called cancer stem cells (CSCs). These studies were conducted mainly on various human cancers; however, isolation and characterization of stem cells from cholangiocarcinoma have not been attempted. The molecular markers CD24, CD44, CD34, and epithelial cell adhesion molecule (EpCAM) are widely used, individually or in combination, to characterize some types of CSCs. In this study, we used these markers to identify a subpopulation of cells in extrahepatic cholangiocarcinoma (ECC) with cancer stem/progenitor cell‐like properties. We found that CD24+CD44+EpCAMhigh cells (0.39–2.27%) were present in human ECC tissues. The expression of a CD24+CD44+EpCAMhigh subpopulation was consistent with primary cancers and could be duplicated during serial in vivo passaging in NOD/SCID mice. CD24+CD44+EpCAMhigh cells isolated from 3 cholangiocarcinoma xenografts showed high tumorigenic potential compared with CD24−CD44−EpCAMlow/− cells. These tumorigenic ECC cells exhibited the stem cell properties of self‐renewal and ability to produce heterogeneous progeny. We report the identification of a CSC population in ECC characterized by CD24, CD44 and EpCAM phenotypes. Our findings could provide new insight into the tumorigenesis of cholangiocarcinoma and offer a potential target for anti‐cancer therapy.