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.

中文翻译：

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空肠弯曲杆菌来源的细胞致死性膨胀毒素促进结直肠癌转移


各种形式的实体瘤都含有细胞内细菌，但这些微生物的生理后果知之甚少。我们表明弯曲杆菌在转移患者的原发性结直肠癌 （CRC） 病变中显着富集。空肠弯曲杆菌衍生的细胞致死性扩张毒素 （CDT） 在肝脏或肺转移小鼠模型中通过 JAK2-STAT3-MMP9 信号传导促进 CRC 转移，这在空肠弯曲 杆菌感染的人结肠组织和 CDT 处理的患者结肠肿瘤样中得到证实。cdtB （ΔcdtB） 或纯化的 CdtB 蛋白的基因缺失表明，基因毒素对于空肠弯曲 杆菌的促转移特性至关重要。在空肠弯曲杆菌定植的小鼠中，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加速转移。总体而言，这些发现表明肿瘤内细菌衍生的基因毒素可加速肿瘤转移，可能为癌症管理开辟新的诊断和治疗途径。