<i>Fusobacterium nucleatum</i>-triggered neutrophil extracellular traps facilitate colorectal carcinoma progression

作者全名："Kong, Xuehua; Zhang, Yu; Xiang, Linwei; You, Yan; Duan, Yaqian; Zhao, Yuqing; Li, Shue; Wu, Rui; Zhang, Jiangbo; Zhou, Lan; Duan, Liang"

作者地址："[Kong, Xuehua; Xiang, Linwei; Zhao, Yuqing; Zhou, Lan] Chongqing Med Univ, Dept Lab Med, Key Lab Diagnost Med, Minist Educ, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Kong, Xuehua; Zhang, Yu; Xiang, Linwei; Duan, Yaqian; Duan, Liang] Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [You, Yan] Chongqing Med Univ, Affiliated Hosp 2, Dept Pathol, Chongqing 400010, Peoples R China; [Li, Shue] Chongqing Med Univ, Affiliated Hosp 2, Dept Acad Res, Chongqing 400010, Peoples R China; [Wu, Rui] Chongqing Med Univ, Affiliated Hosp 1, Dept Lab Med, Chongqing 400016, Peoples R China; [Zhang, Jiangbo] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, Chongqing, Peoples R China"

通信作者："Zhou, L (通讯作者)，Chongqing Med Univ, Dept Lab Med, Key Lab Diagnost Med, Minist Educ, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Duan, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, 74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001064375500001

JCR分区：Q1

影响因子：11.4

年份：2023

卷号：42

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Fusobacterium nucleatum; Colorectal carcinoma; Neutrophil extracellular traps; ROS; TLR4; NOD1/2

摘要："Background Fusobacterium nucleatum (Fn) acts as a procarcinogenic bacterium in colorectal carcinoma (CRC) by regulating the inflammatory tumor microenvironment (TME). Neutrophil extracellular traps (NETs), which can be generated by persistent inflammation, have been recently considered to be significant contributors in promoting cancer progression. However, whether NETs are implicated in Fn-related carcinogenesis is still poorly characterized. Here, we explored the role of NETs in Fn-related CRC as well as their potential clinical significance.Methods Fn was measured in tissue specimens and feces samples from CRC patients. The expression of NET markers were also detected in tissue specimens, freshly isolated neutrophils and blood serum from CRC patients, and the correlation of circulating NETs levels with Fn was evaluated. Cell-based experiments were conducted to investigate the mechanism by which Fn modulates NETs formation. In addition, we clarified the functional mechanism of Fn-induced NETs on the growth and metastasis of CRC in vitro and in vivo experiments.Results Tissue and blood samples from CRC patients, particularly those from Fn-infected CRC patients, exhibited greater neutrophil infiltration and higher NETs levels. Fn infection induced abundant NETs production in in vitro studies. Subsequently, we demonstrated that Fn-induced NETs indirectly accelerated malignant tumor growth through angiopoiesis, and facilitated tumor metastasis, as manifested by epithelial-mesenchymal transition (EMT)-related cell migration, matrix metalloproteinase (MMP)-mediated basement membrane protein degradation, and trapping of CRC cells. Mechanistically, the Toll-like receptor (TLR4)-reactive oxygen species (ROS) signaling pathway and NOD-like receptor (NOD1/2)-dependent signaling were responsible for Fn-stimulated NETs formation. More importantly, circulating NETs combined with carcinoembryonic antigen (CEA) could predict CRC occurrence and metastasis, with areas under the ROC curves (AUCs) of 0.92 and 0.85, respectively.Conclusions Our findings indicated that Fn-induced NETs abundance by activating TLR4-ROS and NOD1/2 signalings in neutrophils facilitated CRC progression. The combination of circulating NETs and CEA was identified as a novel screening strategy for predicting CRC occurrence and metastasis."

基金机构：Not applicable.

基金资助正文：Not applicable.