Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications

Xiang Xia, Zizhen Zhang, Chunchao Zhu, Bo Ni, Shuchang Wang, Shuofei Yang, Fengrong Yu, Enhao Zhao (), Qing Li () and Gang Zhao ()
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Xiang Xia: Shanghai Jiao Tong University
Zizhen Zhang: Shanghai Jiao Tong University
Chunchao Zhu: Shanghai Jiao Tong University
Bo Ni: Shanghai Jiao Tong University
Shuchang Wang: Shanghai Jiao Tong University
Shuofei Yang: Shanghai Jiao Tong University
Fengrong Yu: Shanghai Jiao Tong University
Enhao Zhao: Shanghai Jiao Tong University
Qing Li: Shanghai Jiao Tong University
Gang Zhao: Shanghai Jiao Tong University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Postoperative abdominal infectious complication (AIC) is associated with metastasis in locally advanced gastric cancer (GC) patients after radical gastrectomy. However, the underlying mechanism remains unclear. Herein, we report that neutrophil extracellular traps (NETs), the DNA meshes released by neutrophils in response to infection, could promote GC cells proliferation, invasion, migration and epithelial–mesenchymal transition dependent on TGF-β signaling. Then we model nude mice with cecal puncture without ligation to simulate postoperative AIC and find that NETs in peripheral blood and ascites fluid facilitate GC cells extravasation and implantation into liver and peritoneum for proliferation and metastasis. Notably, TGF-β signaling inhibitor LY 2157299 could effectively impede liver and peritoneal metastasis but not concurrently aggravate sepsis in those AIC-bearing nude mice. These findings implicate that targeting downstream effectors of NETs such as TGF-β signaling might provide potential therapeutic prospect to reduce the risk of GC metastasis.

Date: 2022
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DOI: 10.1038/s41467-022-28492-5

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