Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition.
Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition.
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炎症微环境中的间充质干细胞通过诱导上皮-间质转化加速肝细胞癌转移
DOI：
10.1371/journal.pone.0043272
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Jing Y;Han Z;Liu Y;Sun K;Zhang S;Jiang G;Li R;Gao L;Zhao X;Wu D;Cai X;Wu M;Wei L
在炎症反应中，间充质干细胞（MSC）迁移到组织损伤部位参与免疫调节，组织重塑和伤口愈合。肿瘤对组织施加持续的机械和病理应力，并导致MSC的持续浸润。在这里，我们证明，骨髓间充质干细胞促进人类肝细胞癌（HCC）转移的影响下，炎症。IFN-γ和TNF-α预处理的MSCs培养上清可模拟其促肿瘤转移作用。有趣的是，用上清液处理HCC细胞导致上皮-间充质转化（EMT），这是一种与细胞因子刺激的MSC产生TGFβ相关的效应。重要的是，临床HCC样品中表达SSEA 4的MSC水平与HCC的不良预后显著相关，并且HCC的EMT与较短的无癌间隔（CFI）和较差的总生存期（OS）密切相关。因此，我们的研究结果表明，肿瘤炎症微环境中的MSCs可能通过TGFβ诱导EMT促进肿瘤转移。
In response to inflammation, mesenchymal stem cells (MSCs) are known to migrate to tissue injury sites to participate in immune modulation, tissue remodeling and wound healing. Tumors apply persistent mechanical and pathological stress to tissues and causes continual infiltration of MSCs. Here, we demonstrate that MSCs promote human hepatocellular carcinoma (HCC) metastasis under the influence of inflammation. The metastasis promoting effect could be imitated with the supernatant of MSCs pretreated with IFNγ and TNFα. Interestingly, treatment of HCC cells with the supernatant leads to epithelial-mesenchymal transition (EMT), an effect related to the production of TGFβ by cytokines stimulated MSCs. Importantly, the levels of MSCs expressing SSEA4 in clinical HCC samples significantly correlated with poor prognosis of HCC, and EMT of HCC was strongly associated with a shorter cancer-free interval (CFI) and a worse overall survival (OS). Therefore, our results suggest that MSCs in tumor inflammatory microenvironment could promote tumor metastasis through TGFβ-induced EMT.
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影响因子：
9
作者：
Poon, Ronnie T. P.;Fan, Sheung Tat;Wong, John
通讯作者：
Wong, John
影响因子：
4.6
作者：
Popp, Felix C.;Renner, Philipp;Dahlke, Marc H.
通讯作者：
Dahlke, Marc H.
DOI：
10.1073/pnas.0900244106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Coffelt, Seth B.;Marini, Frank C.;Scandurro, Aline B.
通讯作者：
Scandurro, Aline B.
影响因子：
14
作者：
Quintavalla, J;Uziel-Fusi, S;Pellas, TC
通讯作者：
Pellas, TC
影响因子：
5.7
作者：
Li, Guo-Cai;Ye, Qing-Hai;Qin, Lun-Xiu
通讯作者：
Qin, Lun-Xiu