Yu Jie, Tao Shaolin, Hu Pingping, Wang Ruwen, Fang Chunshu, Xu Yi, Qi Di, Wei Zhuanqin, Zhang Jingge, Tan Qunyou
Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, P. R. China.
J Cancer. 2017 Jul 5;8(11):2060-2068. doi: 10.7150/jca.19069. eCollection 2017.
Lymph node metastasis is still an important issue in metastatic process of lung adenocarcinoma. C-C chemokine receptor 7 (CCR7) has been proved to be closely associated with the metastasis of lung adenocarcinoma, and the mechanism is poorly understood. In order to investigate the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma, and to explore the role of CCR7 in treating lung adenocarcinoma, 40 clinical specimens were collected to define the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma by immunohistochemistry. The siRNA was used to suppress CCR7 expression in A549 cells. The scratch test, transwell test, qRT-PCR, western blot, flow cytometry and immunofluorescence were used to investigate the lymph node metastasis-related function of CCR7 . The athymic mice subcutaneous injection was used to research lung adenocarcinoma formation . Clinical case studies show that higher expression of CCR7 in lung adenocarcinoma tissues was associated with a higher lymph node metastasis. Inhibition of expression of CCR7 can reduce the migration and invasion and suppress the expression of VEGF-C, VEGF-D and VEGF-R3 and . Moreover, CCR7 silence also suppressed WNT and p-ERK pathways . All the results indicate that CCR7 can promote lymph node metastasis in lung adenocarcinoma by regulating VEGF-C/D-R3 pathway. Thus CCR7 is proposed to be a potential prediction for poor prognosis of lung adenocarcinoma, and a therapeutic target for lymph node metastasis.
淋巴结转移仍是肺腺癌转移过程中的一个重要问题。C-C趋化因子受体7(CCR7)已被证明与肺腺癌转移密切相关,但其机制尚不清楚。为了研究CCR7与肺腺癌淋巴结转移之间的关系,并探索CCR7在肺腺癌治疗中的作用,收集了40例临床标本,通过免疫组织化学确定CCR7与肺腺癌淋巴结转移之间的关系。使用小干扰RNA(siRNA)抑制A549细胞中CCR7的表达。采用划痕试验、Transwell试验、实时定量聚合酶链反应(qRT-PCR)、蛋白质免疫印迹法(western blot)、流式细胞术和免疫荧光法研究CCR7与淋巴结转移相关的功能。通过裸鼠皮下注射研究肺腺癌的形成。临床病例研究表明,肺腺癌组织中CCR7的高表达与较高的淋巴结转移相关。抑制CCR7的表达可减少迁移和侵袭,并抑制血管内皮生长因子C(VEGF-C)、血管内皮生长因子D(VEGF-D)和血管内皮生长因子受体3(VEGF-R3)的表达。此外,CCR7沉默还抑制了WNT和磷酸化细胞外信号调节激酶(p-ERK)信号通路。所有结果表明,CCR7可通过调节VEGF-C/D-R3信号通路促进肺腺癌的淋巴结转移。因此,CCR7被认为是肺腺癌预后不良的潜在预测指标,也是淋巴结转移的治疗靶点。