title: Intratumoral neutrophil granulocytes contribute to epithelial-mesenchymal transition in lung adenocarcinoma cells.
abstract: 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-β1 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-β1 was up-regulated and Smad4 translocated into nucleus, indicating that TGF-β/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-β/Smad signal pathway. This may provide mechanistic reasons for why haemoptysis was associated with poor outcome in lung adenocarcinoma.
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.|Department of Radiation Oncology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong, 250014, People's Republic of China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.|Blood Purification Center, Hainan General Hospital, 19 Xiuhua Road, Xiuying District, Haikou, Hainan Province, 570311, People's Republic of China.
authors.forename: Meixiao
authors.initials: M
authors.lastname: Shen
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.
authors.forename: Linhai
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China. dujiajun568@163.com.|Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China. dujiajun568@163.com.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Du
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition; D006098:Granulocytes / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009504:Neutrophils / Q000473:pathology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D016212:Transforming Growth Factor beta; D014746:Vimentin
keywords: Epithelial-mesenchymal transition; Lung adenocarcinoma; Tumor-associated neutrophil