Lung cancer cells release high mobility group box 1 and promote the formation of neutrophil extracellular traps

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

doi:10.3892/ol.2019.10290

Lung cancer cells release high mobility group box 1 and promote the formation of neutrophil extracellular traps

Authors:
- Jiawei Zhou
- Yonglin Yang
- Tingting Gan
- Yan Li
- 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 Diseases, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China, Analysis Center, Nanjing Medical University, Nanjing, Jiangsu 210016, P.R. China, Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 210016, P.R. China
Published online on: April 30, 2019 https://doi.org/10.3892/ol.2019.10290
Pages: 181-188
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer is the leading cause of cancer‑associated mortality. Tumor‑associated neutrophils represent a large portion of inflammatory cells within the lung tumor microenvironment. However, the roles of neutrophil extracellular traps (NETs) in lung cancer remain unclear. In the present study, it was identified that Lewis lung carcinoma cells actively released the danger‑associated molecular pattern protein high mobility group box 1 (HMGB1). Furthermore, HMGB1 in lung cancer cell supernatants promoted the formation of neutrophil extracellular traps (NETs), which was dependent on Toll‑like receptor 4 (TLR4). The downstream molecules of TLR4, including myeloid differentiation factor 88, TIR‑domain‑containing adapter‑inducing interferon‑β, p38 mitogen‑activated protein kinases (p38 MAPKs) and extracellular signal‑regulated kinases (ERKs), were activated during the formation of NETs. In addition, inhibition of p38 MAPKs or ERKs significantly decreased NETs. Morphine, an additional ligand for TLR4, aggravated the NETs induced by lung cancer cells. The present study revealed novel mechanisms in tumor‑associated NET formation.

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