Cancer Stem-Like Cells Accumulated in Nickel-Induced Malignant Transformation. (8th March 2016)

• Record Type: Journal Article
• Authors: Wang, Lei; Fan, Jia; Hitron, John Andrew; Son, Young-Ok; Wise, James T.F.; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Shi, Xianglin
• Is Part Of: Toxicological sciences. Volume 151:Number 2(2016:Jun.)
• Page Start: 376
• Page End: 387
• Publication Date: 2016-03-08
• Subjects: nickel -- carcinogenesis -- cancer stem cells -- superoxide dismutase (SOD) -- reactive oxygen species (ROS); Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfw044
• Languages: English
• ISSNs: 1096-6080

Abstract

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.