Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, China.
Front Immunol. 2023 Apr 20;14:1177604. doi: 10.3389/fimmu.2023.1177604. eCollection 2023.
Neutrophil extracellular traps (NETs) are crucial in the progression of several cancers. The formation of NETs is closely related to reactive oxygen species (ROS), and the granule proteins involved in nucleosome depolymerization under the action of ROS together with the loosened DNA compose the basic structure of NETs. This study aims to investigate the specific mechanisms of NETs promoting gastric cancer metastasis in order to perfect the existing immunotherapy strategies.
In this study, the cells and tumor tissues of gastric cancer were detected by immunological experiments, real-time polymerase chain reaction and cytology experiments. Besides, bioinformatics analysis was used to analyze the correlation between cyclooxygenase-2 (COX-2) and the immune microenvironment of gastric cancer, as well as its effect on immunotherapy.
Examination of clinical specimens showed that NETs were deposited in tumor tissues of patients with gastric cancer and their expression was significantly correlated with tumor staging. Bioinformatics analysis showed that COX-2 was involved in gastric cancer progression and was associated with immune cell infiltration as well as immunotherapy. experiments, we demonstrated that NETs could activate COX-2 through Toll-like receptor 2 (TLR2) and thus enhance the metastatic ability of gastric cancer cells. In addition, in a liver metastasis model of nude mice we also demonstrated the critical role of NETs and COX-2 in the distant metastasis of gastric cancer.
NETs can promote gastric cancer metastasis by initiating COX-2 through TLR2, and COX-2 may become a target for gastric cancer immunotherapy.
中性粒细胞胞外诱捕网（NETs）在多种癌症的进展中起着至关重要的作用。NETs 的形成与活性氧（ROS）密切相关，ROS 作用下参与核小体解聚的颗粒蛋白与松弛的 DNA 一起构成了 NETs 的基本结构。本研究旨在探讨 NETs 促进胃癌转移的具体机制，以期完善现有的免疫治疗策略。
本研究通过免疫实验、实时聚合酶链反应和细胞学实验检测胃癌的细胞和肿瘤组织。此外，还利用生物信息学分析方法分析环氧化酶-2（COX-2）与胃癌免疫微环境的相关性及其对免疫治疗的影响。
临床标本检查表明，NETs 沉积在胃癌患者的肿瘤组织中，其表达与肿瘤分期显著相关。生物信息学分析表明，COX-2 参与胃癌的进展，并与免疫细胞浸润和免疫治疗相关。通过实验，我们证明了 NETs 可以通过 Toll 样受体 2（TLR2）激活 COX-2，从而增强胃癌细胞的转移能力。此外，在裸鼠肝转移模型中，我们还证明了 NETs 和 COX-2 在胃癌远处转移中的关键作用。
NETs 可以通过 TLR2 启动 COX-2 来促进胃癌转移，COX-2 可能成为胃癌免疫治疗的靶点。
