期刊
TUMOR BIOLOGY
卷 36, 期 10, 页码 7789-7796出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-015-3484-1
关键词
Tumor-associated neutrophil; Lung adenocarcinoma; Epithelial-mesenchymal transition
类别
资金
- Shandong Provincial Natural Science Foundation of China [ZR2013HZ001]
- National Natural Science Foundation of China [81301728]
We previously demonstrated that haemoptysis as a prognostic factor in lung adenocarcinoma and haemoptysis was associated with severe vascular invasion and high circulating white blood cell count. Epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion. We hypothesized there was some relationship between tumor-associated inflammatory cells, tumor invasion, EMT, and haemoptysis. Immunohistochemistry (IHC) was used to detect CD66b and E-cadherin expression in tumor tissue. By co-culture tumor cells with polymorphonuclear neutrophils (PMNs), the expressions of EMT markers were assessed by western blotting. TGF-beta 1 concentrations in the supernatant and the migration activities of tumor cells were performed by ELISA and migration assays. Intratumoral CD66b(+) PMN expression was negatively associated with E-cadherin expression. Haemoptysis was significantly associated with neutrophil infiltration (OR = 4.25, 95 % CI 1.246-14.502). Neutrophils promoted EMT of tumor cells in vitro and enhanced the migration activity of tumor cells. In addition, TGF-beta 1 was up-regulated and Smad4 translocated into nucleus, indicating that TGF-beta/Smad signaling pathway was initiated during the process. We indicated that lung adenocarcinoma with haemoptysis was associated with more PMN infiltration and PMNs promoted EMT, partly via TGF-beta/Smad signal pathway. This may provide mechanistic reasons for why haemoptysis was associated with poor outcome in lung adenocarcinoma.
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