Hydrogen Peroxide Promotes Epithelial to Mesenchymal Transition and Stemness in Human Malignant Mesothelioma Cells

Abstract

Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associatedwith asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important processinvolved in the progression of tumors, providing cancer cells with aggressiveness. The present study wasperformed to determine if EMT is induced by H2O2 in human malignant mesothelioma (HMM) cells. CulturedHMM cells were treated with H2O2, followed by measuring expression levels of EMT-related genes and proteins.Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not inepithelioid cells. Treatment of HMM cells with H2O2 promoted EMT, as indicated by increased expression levelsof vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such asOCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with H2O2. Alteration ofthese genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-1α) and transforming growthfactor beta 1 (TGF-β1). Considering that treatment with H2O2 results in excess ROS, the present study suggeststhat oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancingthe expression of stemness genes.