Macrophage-derived soluble factors induce the epithelial-mesenchymal transition of HepG2 cells / 中华肝胆外科杂志

ABSTRACT

Objective This study investigates the epithelial-mesenchymal transition effects exerted on human liver cancer cells HepG2 by THP-1 derived macrophages.The roles of tumor-associated macrophages (TAMs) on liver cancer progression and its mechanisms were explored.Methods HepG2 cells were cultured with THP-1 derived macrophages to mimic the microenvironment of liver cancer.After the culture treatment,morphological changes of the liver cancer cells were observed.Decreased E-cadherin expression is a hallmark of epithelial-mesenchymal transition (EMT),and the Ecadherin protein variations in the HepG2 cells were detected by immunofluorescence (IF) and Westernblot.FlowCytomix was carried out to screen the cytokines in the supernanants of THP-1 cells and THP-1 derived macrophages.Results After culture with macrophages,HepG2 cells revealed a morphological change.These cells lacked epithelial morphology and became a spindle-like mesenchymal cell phenotype.Additionally,the E-cadherin protein expression was reduced dramatically as measured by IF and Western-blot.IL-8 and IL-1β expression in the supernatants were increased 40 and 20 times,respectively,after THP-1 cells were activated to macrophages (P＜0.01).TNF-α expression was increased 8 times (P =0.056).Conclusion THP-1 derived macrophages could induce EMT effects on HepG2 cells,which may relate to the increased secretion of IL-1β,IL-8 and TNF-α.