title: Aberrant cytokine secretion and zinc uptake in chronic cadmium-exposed lung epithelial cells.
abstract: Our previous results showed that cadmium (Cd)-adapted lung epithelial cells (LECs) developed resistance to apoptosis due to non-responsiveness of the c-Jun N-terminal kinase pathway and augmented expression of cytokeratin 8. Since cellular Cd entry is a prerequisite in order for Cd to elicit its cytotoxicity, therefore, we wonder if there are differential metal ion transport ability and also other phenotypic changes that occurred in these Cd-resistant LECs.
  
  
  
  Here, we explored further and found that the zinc (Zn) importer Zip8 was stably abolished in these cells along with a marked decrease of Cd and Zn accumulation. Moreover, by cell migration assays and cytokine antibody array analysis, we found that Cd-adapted cells exhibit enhanced migratory ability possibly due to elevated secretions of vascular endothelial growth factor and macrophage inflammatory protein-3 alpha (MIP-3α).
  
  
  
  Taken together, our results show that during chronic Cd exposure, lung cells antagonize excessive cellular Cd-influx by abolishing Zip8 expression to reduce Cd-toxicity; however, this also renders cells with a diminished Zn uptake. The imbalance of Zn homeostasis and elevation of angiogenic and epithelial-mesenchymal transition-promoting cytokines in Cd-adapted cells might thus likely promote Zn deficiency, angiogenesis, and cell invasion.
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Yan-Ming
authors: YM
authors: Xu
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Yang-Min
authors: YM
authors: Gao
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Dan-Dan
authors: DD
authors: Wu
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Fei-Yuan
authors: FY
authors: Yu
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Zhong-Sheng
authors: ZS
authors: Zang
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Lei
authors: L
authors: Yang
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Yue
authors: Y
authors: Yao
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Na-Li
authors: NL
authors: Cai
authors: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, P. R. China.
authors: Yuan
authors: Y
authors: Zhou
authors: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, P. R. China.
authors: Jen-Fu
authors: JF
authors: Chiu
authors: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, P. R. China.
authors: Yick-Pang
authors: YP
authors: Ching
authors: Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P. R. China.
authors: Andy T Y
authors: AT
authors: Lau
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D057134:Antibodies, Neutralizing / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002104:Cadmium / Q000633:toxicity*; D027682:Cation Transport Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D054418:Chemokine CCL20 / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D015032:Zinc / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; C108355:CCL20 protein, human; D027682:Cation Transport Proteins; D054418:Chemokine CCL20; D016207:Cytokines; C530151:SLC39A8 protein, human; D042461:Vascular Endothelial Growth Factor A; D002104:Cadmium; D015032:Zinc
keywords: Biomarker; Cadmium; MIP-3α; VEGF; Zip8