title: 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 associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by H2O2 in human malignant mesothelioma (HMM) cells. Cultured HMM 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 in epithelioid cells. Treatment of HMM cells with H2O2 promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with H2O2. Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-1α) and transforming growth factor beta 1 (TGF-β1). Considering that treatment with H2O2 results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes.
authors.affiliation: Laboratory of Clinical Pathology, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, South Korea.
authors.forename: Myung-Chul
authors.initials: MC
authors.lastname: Kim
authors.forename: Feng-Ji
authors.initials: FJ
authors.lastname: Cui
authors.forename: Yongbaek
authors.initials: Y
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C497442:HIF1A protein, human; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D016877:Oxidants; C494173:POU5F1 protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D006861:Hydrogen Peroxide