title: Mesenchymal stem cells enhance the metastasis of 3D-cultured hepatocellular carcinoma cells.
abstract: Accumulating evidences have demonstrated that mesenchymal stem cells (MSC) could be recruited to the tumor microenvironment. Umbilical cord mesenchymal stem cells (UCMSC) were attractive vehicles for delivering therapeutic agents against cancer. Nevertheless, the safety of UCMSC in the treatment of tumors including hepatocellular carcinoma (HCC) was still undetermined.
  
  
  
  In this study, an in vitro co-culture system was established to evaluate the effect of UCMSC on the cell growth, cancer stem cell (CSC) characteristics, drug resistance, metastasis of 3D-cultured HCC cells, and the underlying mechanism was also investigated.
  
  
  
  It was found that after co-cultured with UCMSC, the metastatic ability of 3D-cultured HCC cells was significantly enhanced as indicated by up-regulation of matrix metalloproteinase (MMP), epithelial-mesenchymal transition (EMT)-related genes, and migration ability. However, cell growth, drug resistance and CSC-related gene expression of HCC cells were not affected by UCMSC. Moreover, EMT was reversed, MMP-2 expression was down-regulated, and migration ability of HCC cell was significantly inhibited when TGF-β receptor inhibitor SB431542 was added into the co-culture system.
  
  
  
  Therefore, these data indicated that UCMSC could significantly enhance the tumor cell metastasis, which was due to the EMT of HCC cells induced by TGF-β.
authors.affiliation: Laboratory of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Xu
authors.affiliation: Laboratory of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Laboratory of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, People's Republic of China. sungw@dicp.ac.cn.
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Sun
authors.affiliation: Laboratory of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, People's Republic of China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D018920:Coculture Techniques / Q000379:methods*; D004149:Dioxoles / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D009362:Neoplasm Metastasis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D016212:Transforming Growth Factor beta; D020782:Matrix Metalloproteinases; D002945:Cisplatin
keywords: Hepatocellular carcinoma; Metastasis; TGF-β; Three-dimensional cell culture; Umbilical cord mensenchymal stem cells