Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Department of Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Nat Commun. 2022 Feb 23;13(1):1017. doi: 10.1038/s41467-022-28492-5.
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.
术后腹部感染并发症（AIC）与根治性胃切除术后局部晚期胃癌（GC）患者的转移有关。然而，其潜在机制尚不清楚。在此，我们报告中性粒细胞胞外陷阱（NETs），即中性粒细胞在感染时释放的 DNA 网，可通过 TGF-β 信号促进 GC 细胞增殖、侵袭、迁移和上皮间质转化。然后，我们通过盲肠穿刺但不结扎的方法在裸鼠中建立模拟术后 AIC 的模型，发现外周血和腹水的 NETs 促进 GC 细胞渗出并植入肝脏和腹膜，从而促进增殖和转移。值得注意的是，NETs 下游效应物 TGF-β 信号抑制剂 LY 2157299 可有效抑制肝转移和腹膜转移，但不会同时加重 AIC 裸鼠的脓毒症。这些发现表明，针对 NETs 如 TGF-β 信号的下游效应物可能为降低 GC 转移风险提供潜在的治疗前景。
