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

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-beta 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-beta 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-beta signaling might provide potential therapeutic prospect to reduce the risk of GC metastasis. Postoperative abdominal infections have been associated with tumor recurrence and metastasis in patients treated for locally advanced gastric cancer. Here the authors show that infectious complications are associated with the release of neutrophil extracellular traps that facilitate gastric cancer cell extravasation and metastasis formation.

Automated summary

Postoperative abdominal infectious complications are associated with metastasis in gastric cancer, and the release of neutrophil extracellular traps (NETs) by neutrophils can facilitate the extravasation and metastasis formation of gastric cancer cells.