1. Neutrophil Extracellular Traps Facilitate A549 Cell Invasion and Migration in a Macrophage-Maintained Inflammatory Microenvironment
- Author
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Lemeng Zhang, Huifang Yi, Jianhua Chen, Haitao Li, Yongzhong Luo, Tianli Cheng, Hua Yang, Zhou Jiang, and Changqie Pan
- Subjects
Lung Neoplasms ,General Immunology and Microbiology ,Article Subject ,THP-1 Cells ,Macrophages ,General Medicine ,Extracellular Traps ,General Biochemistry, Genetics and Molecular Biology ,A549 Cells ,Cell Movement ,Tumor Microenvironment ,Humans ,Medicine ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Research Article - Abstract
Introduction. The biological functions of neutrophil extracellular traps (NETs) in tumorigenesis have drawn an increasing amount of attention. This study explored the relationship between NETs and the inflammatory microenvironment in lung cancer cell invasion and metastasis. Methods. NETs were quantified using myeloperoxidase (MPO–DNA) and immunofluorescence staining. Cytokine levels were measured using ELISA kits. THP-1 and A549 cells were used for in vitro experiments. Transwell and Matrigel assays were used to assess the invasion and migration abilities of the cells. Results. Neutrophil infiltration and NET formation were observed in the lung cancer tissues. Compared with healthy controls, the level of MPO–DNA complexes in lung cancer patients increased remarkably and was positively correlated with peripheral blood neutrophil counts, smoking status, and poor prognosis. Increased circulating NET levels were also positively correlated with the levels of inflammatory cytokines, including IL-1β, IL-6, IL-18, and TNF-α. Neutrophils isolated from patients with lung cancer are more prone to NET release. NETs can promote the invasion and migration ability of THP-1 and A549 cell in coculture systems, while pretreatment with NET inhibitors can effectively reduce NET-induced invasion and metastasis. The ability of NETs to promote invasion and metastasis is partly dependent on macrophages. Conclusion. Taken together, our study demonstrated that NETs facilitate A549 cell invasion and migration in a macrophage-maintained inflammatory microenvironment.
- Published
- 2022
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