Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma.
Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma.
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DOI：
10.1002/hep.26168
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Yamashita T;Honda M;Nakamoto Y;Baba M;Nio K;Hara Y;Zeng SS;Hayashi T;Kondo M;Takatori H;Yamashita T;Mizukoshi E;Ikeda H;Zen Y;Takamura H;Wang XW;Kaneko S
最近的证据表明，肝细胞癌（HCC）是由具有干细胞特征的细胞亚群（癌症干细胞; CSC）组成的。CSC被认为是根除癌症的关键靶标，并且已经通过使用各种干细胞标记物鉴定了肝脏CSC。然而，目前对标记阳性CSC的表达模式和特征知之甚少，阻碍了个性化CSC靶向治疗的发展。在这里，我们表明CSC标志物EpCAM和CD 90在肝癌中独立表达。在原发性肝癌中，EpCAM+和CD 90+细胞存在明显差异，分选细胞的基因表达分析表明EpCAM细胞具有上皮细胞的特征，而CD 90+细胞具有血管内皮细胞的特征。临床病理分析表明，EpCAM+细胞的存在与低分化形态和高血清甲胎蛋白（AFP），而CD 90+细胞的存在与远处器官转移的高发病率。免疫缺陷小鼠中来自原发性HCC的EpCAM+/CD 90+细胞的连续异种移植揭示了EpCAM+细胞在皮下病变中的快速生长和CD 90+细胞在肺中的高度转移能力。在细胞系中，CD 90+细胞表现出丰富的c-Kit表达和对甲磺酸伊马替尼的体外化疗敏感性。此外，当在体外共培养时，CD 901细胞通过激活转化生长因子β（TGF-β）信号传导增强EpCAM+细胞的运动性，而甲磺酸伊马替尼抑制CD 90+细胞中TGF β 1的表达以及CD 90+细胞诱导的EpCAM+细胞的运动性。我们的数据表明EpCAM+和CD 90 + CSC的离散性和潜在的相互作用，具有特定的基因表达模式和对分子靶向治疗的化学敏感性。不同CSC的存在可能决定HCC的临床结果。
Recent evidence suggests that hepatocellular carcinoma (HCC) is organized by a subset of cells with stem cell features (cancer stem cells; CSCs). CSCs are considered a pivotal target for the eradication of cancer, and liver CSCs have been identified by the use of various stem cell markers. However, little information is known about the expression patterns and characteristics of marker-positive CSCs, hampering the development of personalized CSC-targeted therapy. Here, we show that CSC markers EpCAM and CD90 are independently expressed in liver cancer. In primary HCC, EpCAM+ and CD90+ cells resided distinctively, and gene-expression analysis of sorted cells suggested that EpCAM cells had features of epithelial cells, whereas CD90+ cells had those of vascular endothelial cells. Clinicopathological analysis indicated that the presence of EpCAM+ cells was associated with poorly differentiated morphology and high serum alpha-fetoprotein (AFP), whereas the presence of CD90+ cells was associated with a high incidence of distant organ metastasis. Serial xenotransplantation of EpCAM+/CD90+ cells from primary HCCs in immune-deficient mice revealed rapid growth of EpCAM+ cells in the subcutaneous lesion and a highly metastatic capacity of CD90+ cells in the lung. In cell lines, CD90+ cells showed abundant expression of c-Kit and in vitro chemosensitivity to imatinib mesylate. Furthermore, CD901 cells enhanced the motility of EpCAM+ cells when cocultured in vitro through the activation of transforming growth factor beta (TGF-β) signaling, whereas imatinib mesylate suppressed TGFB1 expression in CD90+ cells as well as CD90+ cell-induced motility of EpCAM+ cells. Our data suggest the discrete nature and potential interaction of EpCAM+ and CD90+ CSCs with specific gene-expression patterns and chemosensitivity to molecular targeted therapy. The presence of distinct CSCs may determine the clinical outcome of HCC.
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影响因子：
64.8
作者：
Ricci-Vitiani, Lucia;Pallini, Roberto;De Maria, Ruggero
通讯作者：
De Maria, Ruggero
影响因子：
50.3
作者：
Ishimoto, Takatsugu;Nagano, Osamu;Saya, Hideyuki
通讯作者：
Saya, Hideyuki
影响因子：
13.5
作者：
Yovchev, Mladen I.;Grozdanov, Petar N.;Dabeva, Mariana D.
通讯作者：
Dabeva, Mariana D.
影响因子：
13.5
作者：
Wang, Yunfang;Yao, Hsin-Lei;Cui, Cal-Bin;Wauthier, Eliane;Barbier, Claire;Costello, Martin J.;Moss, Nicholas;Yamauchi, Mitsuo;Sricholpech, Marnisa;Gerber, David;Loboa, Elizabeth G.;Reid, Lola M.
通讯作者：
Reid, Lola M.
影响因子：
11.2
作者：
Yamashita, Taro;Forgues, Marshorma;Wang, Xin Wei
通讯作者：
Wang, Xin Wei