title: Hepatic stellate cells secretes type I collagen to trigger epithelial mesenchymal transition of hepatoma cells.
abstract: Liver fibrosis is a risk factor for hepatoma. Activated hepatic stellate cells (HSCs) play a critical role in progression of hepatoma. Resected hepatoma patients with high α-SMA+HSCs infiltration had worse survival, OR: 2.2 and p=0.0434. We hypothesized that HSCs could increase the epithelial-mesenchymal transition (EMT) ability of hepatoma cells. In murine model of liver fibrosis with injection of ML1 mice HCC cell line, E-cadherin was lost at the margin of tumor nodule around α-SMA+HSC sites. In subcutaneous tumor model, HSCs could increase the metastatic nodules in the lung, and the expression of E-cadherin was decreased and the Slug was induced. To elucidate the effect of HSCs on hepatoma cells, HSC-T6 was co-cultured with ML1 and the condition medium of HSC-T6 can trigger ML1 cell morphological change, down-expression of E-cadherin, induction of Slug expression, and cell migration. Proteomic analysis of the condition medium showed that collagen I was the target molecule. Collagen type I alone also induced EMT of ML1 cells. Knockdown of collagen type I in HSC-T6 could decrease its induction of EMT on ML1 cells. In conclusion, HSC can secrete collagen type I to trigger hepatoma cells to undergo EMT for metastasis.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University Tainan, Taiwan, China.
authors.forename: Ming-Chen
authors.initials: MC
authors.lastname: Yang
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan, Taiwan, China.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University Tainan, Taiwan, China.
authors.forename: Pao-Chi
authors.initials: PC
authors.lastname: Liao
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan, Taiwan, China.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Yen
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan, Taiwan, China ; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Tainan, Taiwan, China.
authors.forename: Yan-Shen
authors.initials: YS
authors.lastname: Shan
keywords: Hepatic stellate cell; collagen type I; epithelial-mesenchymal transition