Deng Yanlin, Liu Sylvia Yang, Chua Song Lin, Khoo Bee Luan
Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
Biosens Bioelectron. 2021 May 15;180:113113. doi: 10.1016/j.bios.2021.113113. Epub 2021 Feb 27.
Components within the tumor microenvironment, such as intratumoral bacteria (IB; within tumors), affect tumor progression. However, current experimental models have not explored the effects of extratumoral bacteria (EB; outside tumors) on cancer progression. Here, we developed a microfluidic platform to analyze the influence of bacterial distribution on bladder cancer progression under defined conditions, using uropathogenic Escherichia coli. This was achieved by establishing coating (CT) and colonizing (CL) models to simulate the different invasion and colonization modes of IB and EB in tumor tissues. We demonstrated that both EB and IB induced closer cell-cell contacts within the tumor cluster, but cancer cell viability was reduced only in the presence of IB. Interestingly, cancer stem cell counts increased significantly in the presence of EB. These outcomes were due to the formation of extracellular DNA-based biofilms by EB. Triple therapy of DNase (anti-biofilm agent), ciprofloxacin (antibiotic), and doxorubicin (anti-cancer drug) could effectively eradicate biofilms and tumors simultaneously. Our preclinical proof-of-concept provides insights on how bacteria can influence tumor progression and facilitate future research on anti-biofilm cancer management therapies.
肿瘤微环境中的成分，如肿瘤内细菌（IB；肿瘤内部），会影响肿瘤进展。然而，目前的实验模型尚未探究肿瘤外细菌（EB；肿瘤外部）对癌症进展的影响。在此，我们开发了一种微流控平台，使用尿路致病性大肠杆菌，在特定条件下分析细菌分布对膀胱癌进展的影响。这是通过建立包被（CT）和定殖（CL）模型来模拟IB和EB在肿瘤组织中的不同侵袭和定殖模式实现的。我们证明，EB和IB都会在肿瘤簇内诱导更紧密的细胞间接触，但仅在存在IB的情况下癌细胞活力会降低。有趣的是，在存在EB的情况下癌症干细胞数量显著增加。这些结果是由于EB形成了基于细胞外DNA的生物膜。脱氧核糖核酸酶（抗生物膜剂）、环丙沙星（抗生素）和阿霉素（抗癌药物）的三联疗法可有效同时根除生物膜和肿瘤。我们的临床前概念验证为细菌如何影响肿瘤进展提供了见解，并促进了未来抗生物膜癌症管理疗法的研究。
