title: Nickel promotes the invasive potential of human lung cancer cells via TLR4/MyD88 signaling.
abstract: Epidemiological studies have demonstrated a close correlation between nickel exposure and the incidence of lung cancer. Several studies have suggested that nickel contributes to tumor progression of human lung cancer. In this in vitro study, we found that nickel, as nickel chloride, could significantly enhance the invasive potential of human lung cancer cells, accompanied by elevated expression of IL-8, TGF-β, MMP2 and MMP9 in human lung cancer cells. Importantly, we demonstrated that nickel could activate TLR4 signaling in human lung cancer cells. Further studies showed that the TLR4/MyD88 signaling conferred the enhanced invasive potential of human lung cancer cells induced by nickel. Finally, we revealed that the p38MAPK pathway and NF-kB pathway were necessary for the enhanced invasive potential of human lung cancer cells induced by nickel. Our data provide a mechanistic explanation for nickel induced invasion of human lung cancer, and they suggest new strategies for nickel-related lung cancer clinical biotherapies.
authors.affiliation: Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Zengguang
authors.initials: Z
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
authors.forename: Chunyi
authors.initials: C
authors.lastname: Xiao
authors.forename: Huiyi
authors.initials: H
authors.lastname: Li
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D008175:Lung Neoplasms / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009532:Nickel / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; C022838:nickel chloride; D009532:Nickel; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9