2. Academic Validation
  3. Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications

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

  • Nat Commun. 2022 Feb 23;13(1):1017. doi: 10.1038/s41467-022-28492-5.
Xiang Xia  # 1,  Zizhen Zhang  # 1,  Chunchao Zhu  # 1,  Bo Ni 1,  Shuchang Wang 1,  Shuofei Yang 2,  Fengrong Yu 1,  Enhao Zhao 3,  Qing Li 4,  Gang Zhao 5
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
  • 2 Department of Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
  • 3 Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China. zhaoenhao@renji.com.
  • 4 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200240, Shanghai, People's Republic of China. 13851601478@163.com.
  • 5 Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China. zhaogangrj@163.com.
  • # Contributed equally.
PMID: 35197446 DOI: 10.1038/s41467-022-28492-5
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.

Figures
Products