Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling.
Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling.
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DOI：
10.18632/oncotarget.17633
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发表时间：
2017-08-15
期刊：
影响因子：
--
通讯作者：
Lam PYP
中科院分区：
文献类型：
--
作者：
Endaya B;Guan SP;Newman JP;Huynh H;Sia KC;Chong ST;Kok CYL;Chung AYF;Liu BB;Hui KM;Lam PYP
上皮细胞粘附分子（EpCAM）是一种I型跨膜糖蛋白，被认为是人肝细胞癌（HCC）肿瘤起始细胞（TIC）的标志物之一。许多工作都针对这些TICs，作为控制这些细胞增殖和耐药性的主要调节因子的手段。已知人骨髓间充质干细胞表现出肿瘤嗜性的先天性质。然而，MSC和TIC之间可能的关系并不清楚。在这项研究中，我们表明，MSC迁移到HCC可以有效地抑制TACE和γ-分泌酶抑制剂，停止激活EpCAM信号事件。通过siRNA和抗体方法沉默EpCAM表达也导致MSC迁移受损。相比之下，HCC细胞和HCC小鼠异种移植物中EpICD蛋白水平的增加导致MSC迁移增强。总之，这些研究结果表明，MSC被吸引到更具致癌性的HCC群体中，并且可能作为治疗基因的基于细胞的载体，以靶向EpICD富集的肝肿瘤细胞。
The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein that is regarded as one of the markers for tumor initiating cells (TIC) in human hepatocellular carcinoma (HCC). Much work has been directed towards targeting these TICs as a mean of placing these master regulators of cell proliferation and drug resistance under control. Human bone marrow-derived mesenchymal stem cells are known to exhibit an innate property of tumor tropism. However, the possible relationship between MSC and TIC is not well understood. In this study, we show that MSC migration to HCC can be effectively inhibited by TACE and γ-secretase inhibitors that stop the activation of EpCAM signaling event. Silencing of EpCAM expression through siRNA and antibody approaches also resulted in impaired MSC migration. By contrast, increase levels of EpICD proteins in HCC cells and HCC mouse xenografts resulted in enhanced MSC migration. Taken together, these findings show that MSC is drawn to the more oncogenic population of HCC, and could potentially serve as a cell-based carrier of therapeutic genes to target EpICD-enriched hepatic tumor cells.
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影响因子：
64.8
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Lee, Yoonjin;Dominy, John E.;Choi, Yoon Jong;Jurczak, Michael;Tolliday, Nicola;Camporez, Joao Paulo;Chim, Helen;Lim, Ji-Hong;Ruan, Hai-Bin;Yang, Xiaoyong;Vazquez, Francisca;Sicinski, Piotr;Shulman, Gerald I.;Puigserver, Pere
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8
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影响因子：
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作者：
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通讯作者：
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