Macrophages induce EMT to promote invasion of lung cancer cells through the IL-6-mediated COX-2/PGE2/β-catenin signalling pathway

被引:112
作者
Che, Dehai [1 ]
Zhang, Shuai [1 ]
Jing, Zihan [1 ]
Shang, Lihua [1 ]
Jin, Shi [1 ]
Liu, Fang [1 ]
Shen, Jing [1 ]
Li, Yue [1 ]
Hu, Jing [1 ]
Meng, Qingwei [1 ]
Yu, Yan [1 ]
机构
[1] Harbin Med Univ, Canc Hosp, Dept Med Oncol, Hoping Rd 150, Harbin 150081, Heilongjiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Macrophages; EMT; NSCLC; IL-6; COX-2/PGE2; beta-catenin; TUMOR-ASSOCIATED MACROPHAGES; TO-MESENCHYMAL TRANSITION; BREAST-CANCER; PROSTAGLANDIN E-2; BETA-CATENIN; COX-2; EXPRESSION; IN-VITRO; CYCLOOXYGENASE-2; ANGIOGENESIS; CARCINOMA;
D O I
10.1016/j.molimm.2017.06.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Infiltration of macrophages plays a critical role in the connection between inflammation and cancer invasion; however, the molecular mechanism that enables this crosstalk remains unclear. This paper investigates a molecular link between infiltration of macrophages and metastasis of lung cancer cells. In this study, the macrophage density and cyclooxygenase-2 (COX-2) protein were examined in surgical specimens by immunohistochemistry (IIIC), and the prostaglandin E2 (PGE2) levels were determined in the blood of 30 non-small cell lung cancer (NSCLC) patients using enzyme-linked immunosorbent assay (ELISA). We demonstrated that macrophage infiltration was significantly associated with elevated tumour COX-2 expression and serum PGE2 levels in NSCLC patients. Interestingly, the COX-2 and PGE2 levels as well as macrophages were poor predictors of NSCLC patient survival. THP-1-derived macrophages were co-cultured in vitro with A549 and H1299 lung cancer cells. In the co-culture process, interleukin-6 (IL-6) induced the COX-2/PGE2 pathway in lung cancer cells, which subsequently promoted A-catenin translocation from the cytoplasm to the nucleus, resulting in epithelial-mesenchymal transition (EMT) and lung cancer cell invasion. Our findings show that the IL-6-dependent COX-2/PGE2 pathway induces EMT to promote invasion of tumour cells through beta-catenin activation during the interaction between macrophages and lung cancer cells, which suggests that inhibition of COX-2/PGE2 or macrophages has the potential to suppress metastasis of lung cancer cells.
引用
收藏
页码:197 / 210
页数:14
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