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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aged
-
Carcinoma, Hepatocellular / physiopathology*
-
Cytokines / metabolism
-
Epithelial-Mesenchymal Transition
-
Female
-
Humans
-
Inflammation / pathology*
-
Liver Neoplasms / physiopathology*
-
Male
-
Mesenchymal Stem Cells / cytology*
-
Middle Aged
-
Multivariate Analysis
-
Neoplasm Metastasis
-
Phenotype
-
Proportional Hazards Models
-
Transforming Growth Factor beta / metabolism
-
Treatment Outcome
-
Wound Healing
Substances
-
Cytokines
-
Transforming Growth Factor beta
Grants and funding
This project was supported by Key project of National Natural Science Foundation of China (grant no: 81030041); Key Basic Research Project of China (grant no: 2010CB945600, 2011CB966200); National Natural Science Foundation of China (grant no: 30901722, 31171321, 81000970,81101622); Special Funds for National key Sci-Tech Special Project of China (grant no: 2008ZX10002-019, 2008ZX10002-025); Shanghai Science and Technology Committee (grant no: 10ZR1439600, 11ZR1449500, 10411963100, 10ZR1439900) and Science Fund for Creative Research Groups, NSFC, China (grant no: 30921006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.