Journal
PROTEOMICS CLINICAL APPLICATIONS
Volume 11, Issue 3-4, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/prca.201600059
Keywords
Biomarker; Cadmium; MIP-3 alpha; VEGF; Zip8
Funding
- National Natural Science Foundation of China [31170785, 31271445]
- Fund for University Talents of Guangdong Province
- Guangdong Natural Science Foundation of China [S2012030006289]
- Department of Education
- Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases
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Purpose: 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. Experimental design and results: 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-3 alpha). Conclusion and clinical relevance: 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.
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