Liu Yao, Wang Jing, Ni Ting, Wang Lihua, Wang Yudong, Sun Xiao
Department of Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Laboratory for Gynecologic Oncology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Oncotarget. 2016 May 3;7(18):25328-39. doi: 10.18632/oncotarget.8291.
RANK/RANKL facilitates migration/invasion via epithelial-mesenchymal transition (EMT) in certain malignant tumors. The relationship and mechanism between RANK/RANKL and EMT in endometrial cancer (EC) cells, however, remain unclear. In this study, we firstly showed that RANK/RANKL activation was correlated with EC staging and EMT markers in human EC tissue specimen. RANK/RANKL promoted migration/invasion and initiated EMT of EC cell lines. Then, protein chip analysis and enzyme-linked immunosorbent assay (ELISA) revealed that the expression and secretion of chemokine ligand 20 (CCL20) was dramatically enhanced in RANKL-treated RANK over-expressed EC cells. Moreover, the higher level of CCL20 in both serum and tumor tissue was detected in orthotopic transplantation mouse models. Finally, we confirmed that CCL20 contributed to invasion and EMT of RANK over-expressed EC cells. In summary, all data supported the hypothesis that RANK/RANKL elevated the expression and secretion of CCL20 in EC cells, which promoted cancer progression through EMT.
RANK/RANKL通过上皮-间质转化（EMT）促进某些恶性肿瘤的迁移/侵袭。然而，RANK/RANKL与子宫内膜癌（EC）细胞中EMT之间的关系及机制仍不清楚。在本研究中，我们首先表明RANK/RANKL激活与人类EC组织标本中的EC分期和EMT标志物相关。RANK/RANKL促进EC细胞系的迁移/侵袭并启动EMT。然后，蛋白质芯片分析和酶联免疫吸附测定（ELISA）显示，在RANKL处理的RANK过表达的EC细胞中，趋化因子配体20（CCL20）的表达和分泌显著增强。此外，在原位移植小鼠模型中检测到血清和肿瘤组织中CCL20水平较高。最后，我们证实CCL20促进了RANK过表达的EC细胞的侵袭和EMT。总之，所有数据支持以下假设：RANK/RANKL提高了EC细胞中CCL20的表达和分泌，通过EMT促进癌症进展。
