He Zhen, Yu Jing, Gong Junli, Wu Jinjie, Zong Xuan, Luo Zhanhao, He Xiaowen, Cheng Wai Ming, Liu Yugeng, Liu Chen, Zhang Qiang, Dai Lei, Ding Tao, Gao Beile, Gharaibeh Raad Z, Huang Jinlin, Jobin Christian, Lan Ping
Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510655, China.
Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510655, China.
Cell Host Microbe. 2024 Dec 11;32(12):2080-2091.e6. doi: 10.1016/j.chom.2024.11.006. Epub 2024 Dec 2.
Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB (ΔcdtB) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni's pro-metastatic property. In C.-jejuni-colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.
多种实体瘤中都存在细胞内细菌，但这些微生物的生理影响却鲜为人知。我们发现，在有转移的患者的原发性结直肠癌（CRC）病变中，弯曲杆菌显著富集。在肝或肺转移小鼠模型中，空肠弯曲杆菌衍生的细胞致死性膨胀毒素（CDT）通过JAK2-STAT3-MMP9信号通路促进CRC转移，在空肠弯曲杆菌感染的人结肠组织和患者的CDT处理的结肠类肿瘤中也得到了证实。cdtB基因缺失（ΔcdtB）或纯化的CdtB蛋白表明，基因毒素对于空肠弯曲杆菌的促转移特性至关重要。在空肠弯曲杆菌定殖的小鼠中，产生CDT的空肠弯曲杆菌向肠外植入肿瘤的易位增加，可能导致这些肿瘤的转移加速。总体而言，这些发现表明，肿瘤内细菌衍生的基因毒素会加速肿瘤转移，这可能为癌症治疗开辟新的诊断和治疗途径。
