Li Baimou, Mao Xiaopeng, Wang Hua, Su Guanyu, Mo Chengqiang, Cao Kaiyuan, Qiu Shaopeng
Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
Research Center for Clinical Laboratory Standard, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
Oncol Lett. 2018 Apr;15(4):5193-5200. doi: 10.3892/ol.2018.7975. Epub 2018 Feb 7.
The aim of the present study was to investigate the associations between vasculogenic mimicry (VM) and zinc finger E-box binding homeobox 1 (ZEB1) in bladder cancer. VM structure and ZEB1 expression were analyzed by cluster of differentiation 34/periodic acid Schiff (PAS) double staining and immunohistochemical staining in 135 specimens from patients with bladder cancer, and a further 12 specimens from normal bladder tissues. Three-dimensional (3-D) culture was used to detect VM formation in the bladder transitional cancer cell lines UM-UC-3 and J82, and the immortalized human bladder epithelium cell line SV-HUC-1 . ZEB1 expression in these cell lines was compared by reverse transcription-quantitative polymerase chain reaction and western blot assays. In addition, small interfering RNA was used to inhibit ZEB1 in UM-UC-3 and J82 cells, followed by 3-D culturing of treated cell lines. As a result, VM was observed in 31.1% of specimens from bladder cancer tissues, and cases with high ZEB1 expression accounted for 60.0% of patients with bladder cancer. In addition, ZEB1 expression was closely associated with VM (r=0.189; P<0.05), and also increased as the grade and stage of the tumor developed. In an assay, UM-UC-3 and J82 cells exhibited VM formation, however, SV-HUC-1 did not. Furthermore, VM-forming cancer cell lines UM-UC-3 and J82 exhibited higher ZEB1 expression. Notably, VM formation was inhibited following knockdown of ZEB1. In conclusion, ZEB1 may be associated with VM in bladder cancer and serve an important role in the process of VM formation. However, its detailed mechanism requires further study.
本研究旨在探讨血管生成拟态（VM）与锌指E盒结合同源框1（ZEB1）在膀胱癌中的相关性。采用分化簇34/过碘酸希夫（PAS）双重染色和免疫组织化学染色法，对135例膀胱癌患者的标本以及另外12例正常膀胱组织标本进行VM结构和ZEB1表达分析。利用三维（3-D）培养检测膀胱移行癌细胞系UM-UC-3和J82以及永生化人膀胱上皮细胞系SV-HUC-1中的VM形成。通过逆转录定量聚合酶链反应和蛋白质免疫印迹法比较这些细胞系中ZEB1的表达。此外，使用小干扰RNA抑制UM-UC-3和J82细胞中的ZEB1，随后对处理后的细胞系进行3-D培养。结果显示，31.1%的膀胱癌组织标本中观察到VM，ZEB1高表达的病例占膀胱癌患者的60.0%。此外，ZEB1表达与VM密切相关（r=0.189；P<0.05），并且随着肿瘤分级和分期的发展而增加。在一项实验中，UM-UC-3和J82细胞表现出VM形成，然而，SV-HUC-1细胞未表现出VM形成。此外，形成VM的癌细胞系UM-UC-3和J82表现出更高的ZEB1表达。值得注意的是，ZEB1敲低后VM形成受到抑制。总之，ZEB1可能与膀胱癌中的VM相关，并在VM形成过程中起重要作用。然而，其详细机制需要进一步研究。
