Researches Department, Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Botany and Microbiology Department, Faculty of Science, Cairo University, Giza, Egypt.
Sci Rep. 2020 Oct 22;10(1):18024. doi: 10.1038/s41598-020-74390-5.
Bacteria is recognized as opportunistic tumor inhabitant, giving rise to an environmental stress that may alter tumor microenvironment, which directs cancer behavior. In vitro infection of the T24 cell line with E. coli was performed to study the bacterial impact on bladder cancer cells. EMT markers were assessed using immunohistochemistry, western blot and RT-PCR. Stemness characteristics were monitored using RT-PCR. Furthermore, the metabolic reprograming was investigated by detection of ROS and metabolic markers. A significant (p ≤ 0.001) upregulation of vimentin as well as downregulation of CK19 transcription and protein levels was reported. A significant increase (p ≤ 0.001) in the expression level of stemness markers (CD44, NANOG, SOX2 and OCT4) was reported. ROS level was elevated, that led to a significant increase (p ≤ 0.001) in UCP2. This enhanced a significant increase (p ≤ 0.001) in PDK1 to significantly downregulate PDH (p ≤ 0.001) in order to block oxidative phosphorylation in favor of glycolysis. This resulted in a significant decrease (p ≤ 0.001) of AMPK, and a significant elevation (p ≤ 0.001) of MCT1 to export the produced lactate to extracellular matrix. Thus, bacteria may induce alteration to the heterogonous tumor cell population through EMT, CSCs and metabolic reprogramming, which may improve cancer cell ability to migrate and self-renew.
细菌被认为是机会性肿瘤寄居者，导致肿瘤微环境发生变化，从而改变肿瘤的行为。通过体外感染 T24 细胞系来研究大肠杆菌对膀胱癌细胞的影响。通过免疫组织化学、western blot 和 RT-PCR 评估 EMT 标志物。通过 RT-PCR 监测干性特征。此外，通过检测 ROS 和代谢标志物研究代谢重编程。报道称，波形蛋白的表达显著上调（p≤0.001），而 CK19 转录和蛋白水平显著下调。报道称干性标志物（CD44、NANOG、SOX2 和 OCT4）的表达水平显著增加（p≤0.001）。ROS 水平升高，导致 UCP2 显著增加（p≤0.001）。这显著增加了 PDK1（p≤0.001），从而显著下调 PDH（p≤0.001），以阻止氧化磷酸化，有利于糖酵解。这导致 AMPK 显著减少（p≤0.001），MCT1 显著升高（p≤0.001），将产生的乳酸输出到细胞外基质。因此，细菌可能通过 EMT、CSCs 和代谢重编程诱导肿瘤异质性细胞群体的改变，从而提高癌细胞的迁移和自我更新能力。
