title: Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition.
abstract: 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.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Jing
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.forename: Guocheng
authors.initials: G
authors.lastname: Jiang
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.forename: Xiong
authors.initials: X
authors.lastname: Cai
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008113:Liver Neoplasms / Q000503:physiopathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D010641:Phenotype; D016016:Proportional Hazards Models; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome; D014945:Wound Healing
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta