Department of Surgery, Division of Surgical Oncology, University of Illinois College of Medicine, Chicago, IL, 60612, USA.
Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Commun Biol. 2023 Jan 6;6(1):16. doi: 10.1038/s42003-022-04395-5.
Microorganisms living at many sites in the human body compose a complex and dynamic community. Accumulating evidence suggests a significant role for microorganisms in cancer, and therapies that incorporate bacteria have been tried in various types of cancer. We previously demonstrated that cupredoxin azurin secreted by the opportunistic pathogen Pseudomonas aeruginosa, enters human cancer cells and induces apoptotic death. However, the physiological interactions between P. aeruginosa and humans and their role in tumor homeostasis are largely unknown. Here, we show that P. aeruginosa upregulated azurin secretion in response to increasing numbers of and proximity to cancer cells. Conversely, cancer cells upregulated aldolase A secretion in response to increasing proximity to P. aeruginosa, which also correlated with enhanced P. aeruginosa adherence to cancer cells. Additionally, we show that cancer patients had detectable P. aeruginosa and azurin in their tumors and exhibited increased overall survival when they did, and that azurin administration reduced tumor growth in transgenic mice. Our results suggest host-bacterial symbiotic mutualism acting as a diverse adjunct to the host defense system via inter-kingdom communication mediated by the evolutionarily conserved proteins azurin and human aldolase A. This improved understanding of the symbiotic relationship of bacteria with humans indicates the potential contribution to tumor homeostasis.
人体许多部位的微生物构成了一个复杂而动态的群落。越来越多的证据表明微生物在癌症中起重要作用，并且已经尝试了将细菌纳入各种类型癌症的治疗方法。我们之前证明，机会性病原体铜蓝蛋白假单胞菌分泌的铜蓝蛋白进入人类癌细胞并诱导细胞凋亡。然而，铜绿假单胞菌与人类之间的生理相互作用及其在肿瘤动态平衡中的作用在很大程度上是未知的。在这里，我们表明铜绿假单胞菌响应癌细胞数量的增加和与癌细胞的接近程度而上调铜蓝蛋白的分泌。相反，癌细胞响应与铜绿假单胞菌的接近程度而上调醛缩酶 A 的分泌，这也与增强铜绿假单胞菌对癌细胞的粘附相关。此外，我们表明癌症患者的肿瘤中可检测到铜绿假单胞菌和铜蓝蛋白，并表现出更高的总体生存率，而铜蓝蛋白的给药可减少转基因小鼠的肿瘤生长。我们的研究结果表明，宿主-细菌共生关系通过进化上保守的铜蓝蛋白和人醛缩酶 A 介导的跨物种通讯作为宿主防御系统的多样化辅助，发挥作用。对细菌与人类共生关系的这种更好理解表明了其对肿瘤动态平衡的潜在贡献。
