EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features.
EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features.
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DOI：
10.1053/j.gastro.2008.12.004
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发表时间：
2009-03
期刊：
影响因子：
29.4
通讯作者：
Wang XW
中科院分区：
文献类型：
--
作者：
Yamashita T;Ji J;Budhu A;Forgues M;Yang W;Wang HY;Jia H;Ye Q;Qin LX;Wauthier E;Reid LM;Minato H;Honda M;Kaneko S;Tang ZY;Wang XW
癌症进展/转移和胚胎发育具有许多共同特性，包括细胞可塑性、动态细胞运动以及与微环境的整体相互作用。我们假设肝细胞癌（HCC）的异质性可能部分是由于具有干/祖细胞特征的肝癌细胞的存在。使用基因表达谱和免疫组织化学分析来分析来自最近确定的两种 HCC 亚型（EpCAM+ AFP+ HCC 和 EpCAM−AFP− HCC）的 235 个肿瘤样本。这些亚型的差异在于甲胎蛋白 (AFP)（一种在发育中的胚胎中产生的分子）和 EpCAM（一种细胞表面肝干细胞标记物）的表达。使用荧光激活细胞分选 (FACS) 分离 EpCAM+ HCC 细胞，并测试其肝干/祖细胞特性。基因表达和通路分析显示EpCAM+AFP+HCC亚型具有肝干/祖细胞的特征。事实上，FACS 分离的 EpCAM+ HCC 细胞表现出肝癌干细胞样特征，包括自我更新和分化的能力。此外，这些细胞能够在 NOD/SCID 小鼠中引发高度侵袭性的 HCC。 Wnt/β-连环蛋白信号传导的激活丰富了 EpCAM+ 细胞群，而基于 RNA 干扰的 EpCAM（Wnt/β-连环蛋白信号传导靶点）阻断则减弱了这些细胞的活性。综上所述，我们的结果表明，HCC 的生长和侵袭性是由 EpCAM+ 细胞的子集决定的，通过靶向 Wnt/β-连环蛋白信号成分（如 EpCAM），为根除 HCC 癌细胞开辟了新途径。
Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC) may be, in part, due to the presence of hepatic cancer cells with stem/progenitor features. Gene expression profiling and immunohistochemistry analyses were used to analyze 235 tumor specimens derived from two recently identified HCC subtypes (EpCAM+ AFP+ HCC and EpCAM− AFP− HCC). These subtypes differed in their expression of alpha-fetoprotein (AFP), a molecule produced in the developing embryo, and EpCAM, a cell surface hepatic stem cell marker. Fluorescence-activated cell sorting (FACS) was used to isolate EpCAM+ HCC cells, which were tested for hepatic stem/progenitor cell properties. Gene expression and pathway analyses revealed that the EpCAM+ AFP+ HCC subtype had features of hepatic stem/progenitor cells. Indeed, the FACS-isolated EpCAM+ HCC cells displayed hepatic cancer stem cell-like traits including the abilities to self-renew and differentiate. Moreover, these cells were capable of initiating highly invasive HCC in NOD/SCID mice. Activation of Wnt/β-catenin signaling enriched the EpCAM+ cell population, while RNA interference-based blockage of EpCAM, a Wnt/β-catenin signaling target, attenuated the activities of these cells. Taken together, our results suggest that HCC growth and invasiveness is dictated by a subset of EpCAM+ cells, opening a new avenue for HCC cancer cell eradication by targeting Wnt/β-catenin signaling components such as EpCAM.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
64.8
作者：
Reya, T;Clevers, H
通讯作者：
Clevers, H