Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
Int J Oncol. 2019 May;54(5):1555-1566. doi: 10.3892/ijo.2019.4729. Epub 2019 Feb 27.
Although important progress has been made in elucidating the role of the tumor microenvironment in the development of bladder cancer, little is currently known regarding the interactions with vascular endothelial cells (ECs) that promote cancer progression. In the present study, it is reported that epidermal growth factor receptor ligands induced by the upregulation of vascular endothelial growth factor (VEGF)‑A and VEGF‑C via the VEGF receptor (R)2/nuclear factor‑κB signaling pathway in ECs, may trigger EGFR signaling in bladder cancer cells and promote bladder cancer progression. Furthermore, the interaction between bladder cancer cells and ECs enhanced EC recruitment though the CXCL1/CXCL5/CXCL8‑CXCR2 pathway. Western blotting was used to evaluate the presence of VEGFR, EGFR and nuclear factor‑κB, and reverse transcription‑quantitative polymerase chain reaction was used to evaluate the expression of VEGFR ligands and EGFR ligands. The present results indicate the mechanism by which the indirect interplay between bladder cancer cells and vascular ECs promotes cancer progression, through the VEGFR2 signaling pathway in vascular ECs and through the EGFR signaling pathway in bladder cancer cells.
虽然在阐明肿瘤微环境在膀胱癌发展中的作用方面已经取得了重要进展,但目前对于促进癌症进展的与血管内皮细胞 (ECs) 的相互作用知之甚少。在本研究中,据报道,ECs 中血管内皮生长因子 (VEGF)-A 和 VEGF-C 通过 VEGF 受体 (R)2/核因子-κB 信号通路的上调诱导的表皮生长因子受体 (EGFR) 配体,可能触发膀胱癌细胞中的 EGFR 信号通路并促进膀胱癌进展。此外,膀胱癌细胞与 ECs 之间的相互作用通过 CXCL1/CXCL5/CXCL8-CXCR2 途径增强了 EC 的募集。通过 Western blot 分析评估 VEGFR、EGFR 和核因子-κB 的存在,通过逆转录-定量聚合酶链反应评估 VEGFR 配体和 EGFR 配体的表达。本研究结果表明,膀胱癌细胞与血管 ECs 之间的间接相互作用通过血管 ECs 中的 VEGFR2 信号通路以及膀胱癌细胞中的 EGFR 信号通路促进癌症进展的机制。