Extracellular RNAs from lung cancer cells activate epithelial cells and induce neutrophil extracellular traps

Li,Yan; Yang,Yonglin; Gan,Tingting; Zhou,Jiawei; Hu,Fan; Hao,Nannan; Yuan,Baorui; Chen,Yu; Zhang,Mingshun

doi:10.3892/ijo.2019.4808

Extracellular RNAs from lung cancer cells activate epithelial cells and induce neutrophil extracellular traps

Authors:
- Yan Li
- Yonglin Yang
- Tingting Gan
- Jiawei Zhou
- Fan Hu
- Nannan Hao
- Baorui Yuan
- Yu Chen
- Mingshun Zhang
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Affiliations: Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Infectious Disease, Nanjing Medical University Nanjing First Hospital, Nanjing, Jiangsu 210006, P.R. China, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 210016, P.R. China, Key Laboratory of Antibody Technique of Health Ministry, Nanjing Medical University, Nanjing, Jiangsu 210016, P.R. China
Published online on: May 21, 2019 https://doi.org/10.3892/ijo.2019.4808
Pages: 69-80
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neutrophil infiltration is frequently observed in lung cancer tissues. Extracellular RNAs (exRNAs) may facilitate tumor progression. The present study investigated the cross‑talk of tumor exRNAs and neutrophil extracellular traps (NETs) in lung cancer. Lewis lung carcinoma (LLC) cells were cultured with the deprived sera. And the cell culture supernatants (CCS) were analyzed in vitro and in vivo. The results revealed that exRNAs from lung cancer CCS promoted the inflammatory cytokine interleukin‑1β and reduced the vascular cell adhesion molecule‑1 expression in lung epithelial cells. Lung cancer CCS‑treated epithelial cells induced the production of NETs. By contrast, NETs reduced the tight junction protein claudin‑5 in epithelial cells. Furthermore, NETs caused the necrosis of epithelial cells, which resulted in the release of exRNAs. In mice, lung cancer cells instilled in the lung recruited neutrophils and initiated NETs. In patients with lung cancer, NETs were also observed. These results suggested that exRNAs in the cell culture supernatant may indirectly induce NETs and contribute to lung cancer oncogenesis.

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