Mesenchymal Stem Cells in Inflammation Microenvironment Accelerates Hepatocellular Carcinoma Metastasis by Inducing Epithelial-Mesenchymal Transition

被引：86

作者：

Jing, Yingying ^{[1
]}

Han, Zhipeng ^{[1
]}

Liu, Yan ^{[1
]}

Sun, Kai ^{[1
]}

Zhang, Shanshan ^{[1
]}

Jiang, Guocheng ^{[1
]}

Li, Rong ^{[1
]}

Gao, Lu ^{[1
]}

Zhao, Xue ^{[1
]}

Wu, Dong ^{[2
]}

Cai, Xiong ^{[2
]}

Wu, Mengchao ^{[1
]}

Wei, Lixin ^{[1
]}

机构：

[1] Second Mil Med Univ, Tumor Immunol & Gene Therapy Ctr, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China

[2] Second Mil Med Univ, Dept Combined Treatment, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China

来源：

PLOS ONE | 2012年 / 7卷 / 08期

基金：

中国国家自然科学基金;

关键词：

T-LYMPHOCYTE PROLIFERATION; BONE-MARROW; STROMAL CELLS; TGF-BETA; EXPRESSION; CANCER; GROWTH; TRANSPLANTATION; PROGRESSION;

D O I：

10.1371/journal.pone.0043272

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 IFN gamma and TNF alpha. Interestingly, treatment of HCC cells with the supernatant leads to epithelial-mesenchymal transition (EMT), an effect related to the production of TGF beta 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 TGF beta-induced EMT.

引用

页数：13

共 34 条

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