title: Cancer Stem-Like Cells Accumulated in Nickel-Induced Malignant Transformation.
abstract: Nickel compounds are known as human carcinogens. Chronic environmental exposure to nickel is a worldwide health concern. Although the mechanisms of nickel-induced carcinogenesis are not well understood, recent studies suggest that stem cells/cancer stem cells are likely important targets. This study examines the role of cancer stem cells in nickel-induced cell transformation. The nontransformed human bronchial epithelial cell line (Beas-2B) was chronically exposed to nickel chloride for 12 months to induce cell transformation. Nickel induced Beas-2B cell transformation, and cancer stem-like cells were enriched in nickel-transformed cell (BNiT) population. The BNiT cancer stem-like cells demonstrated enhanced self-renewal and distinctive differentiation properties. In vivo tumorigenesis studies show that BNiT cancer stem-like cells possess a high tumor-initiating capability. It was also demonstrated that superoxide dismutase 1 was involved in the accumulation of cancer stem-like cells; the regulation of superoxide dismutase 1 expression was different in transformed stem-like cells and nontransformed. Overall, the accumulation of stem-like cells and their enhanced stemness functions contribute to nickel-induced tumorigenesis. Our study provides additional insight into the mechanisms by which metals or other chemicals can induce carcinogenesis.
authors.affiliation: *Center for Research on Environmental Disease Toxicology and Cancer Biology, and.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Toxicology and Cancer Biology, and.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: Toxicology and Cancer Biology, and.
authors.forename: John Andrew
authors.initials: JA
authors.lastname: Hitron
authors.affiliation: *Center for Research on Environmental Disease Toxicology and Cancer Biology, and.
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Son
authors.affiliation: Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, Kentucky 40536.
authors.forename: James T F
authors.initials: JT
authors.lastname: Wise
authors.affiliation: *Center for Research on Environmental Disease Toxicology and Cancer Biology, and.
authors.forename: Ram Vinod
authors.initials: RV
authors.lastname: Roy
authors.affiliation: Toxicology and Cancer Biology, and.
authors.forename: Donghern
authors.initials: D
authors.lastname: Kim
authors.affiliation: Toxicology and Cancer Biology, and.
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.affiliation: *Center for Research on Environmental Disease Toxicology and Cancer Biology, and.
authors.forename: Poyil
authors.initials: P
authors.lastname: Pratheeshkumar
authors.affiliation: Toxicology and Cancer Biology, and.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: *Center for Research on Environmental Disease Toxicology and Cancer Biology, and xshi5@uky.edu.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D000066673:Cell Self Renewal / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D009532:Nickel / Q000633:toxicity*; D010641:Phenotype; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; C000606290:SOD1 protein, human; C022838:nickel chloride; D009532:Nickel; D000072105:Superoxide Dismutase-1
keywords: cancer stem cells; carcinogenesis; nickel; reactive oxygen species (ROS); superoxide dismutase (SOD)