Document Detail


Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition.
MedLine Citation:
PMID:  22952657     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Yingying Jing; Zhipeng Han; Yan Liu; Kai Sun; Shanshan Zhang; Guocheng Jiang; Rong Li; Lu Gao; Xue Zhao; Dong Wu; Xiong Cai; Mengchao Wu; Lixin Wei
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-28
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-09-06     Completed Date:  2013-02-19     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e43272     Citation Subset:  IM    
Affiliation:
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Aged
Carcinoma, Hepatocellular / physiopathology*
Cytokines / metabolism
Epithelial-Mesenchymal Transition
Female
Humans
Inflammation / pathology*
Liver Neoplasms / physiopathology*
Male
Mesenchymal Stromal Cells / cytology*
Middle Aged
Multivariate Analysis
Neoplasm Metastasis
Phenotype
Proportional Hazards Models
Transforming Growth Factor beta / metabolism
Treatment Outcome
Wound Healing
Chemical
Reg. No./Substance:
0/Cytokines; 0/Transforming Growth Factor beta
Comments/Corrections

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