title: Prostaglandin E2 upregulates β1 integrin expression via the E prostanoid 1 receptor/nuclear factor κ-light-chain-enhancer of activated B cells pathway in non-small-cell lung cancer cells.
abstract: The prostaglandin E2 (PGE2) E prostanoid (EP)1 receptor shown to be associated with lung cancer cell invasion. However, the mechanism of EP1 receptor-mediated cell migration remains to be elucidated. β1 integrin is an essential regulator of the tumorigenic properties of non-small-cell lung carcinoma (NSCLC) cells. To date, little is known regarding the association between the EP1 receptor and β1 integrin expression. The present study investigated the effect of EP1 receptor activation on β1 integrin expression and cell migration in NSCLC cells. A total of 34 patients with clinical diagnosis of NSCLC and 10 patients with benign disease were recruited for the present study. The expression levels of the EP1 receptor and β1 integrin expression were studied in resected lung tissue using immunohistochemistry. A statistical analysis was performed using Stata se12.0 software. The effects of PGE2, EP1 agonist 17-phenyl trinor-PGE2 (17-PT-PGE2) and the nuclear factor κ-B (NF-κB) inhibitor on β1 integrin expression were investigated on A549 cells. The expression of β1 integrin and the phosphorylation of NF-κB‑p65 Ser536 was investigated by western blot analysis. Cell migration was assessed by a transwell assay. The results demonstrated that β1 integrin and EP1 receptor expression exhibited a positive correlation of evident significance in the 44 samples. The in vitro migration assay revealed that cell migration was increased by 30% when the cells were treated with 5 µM 17-PT-PGE2 and that the pre-treatment of β1 integrin monoclonal antibody inhibited 17-PT-PGE2‑mediated cell migration completely. PGE2 and 17-PT-PGE2 treatment increased β1 integrin expression. RNA interference against the EP1 receptor blocked the PGE2-mediated β1 integrin expression in A549 cells. Treatment with 17-PT-PGE2 induced NF-κB activation, and the selective NF-κB inhibitor pyrrolidinedithiocarbamate inhibited 17-PT-PGE2-mediated β1 integrin expression. In conclusion, the present study indicated that the PGE2 EP1 receptor regulates β1 integrin expression and cell migration in NSCLC cells by activating the NF-κB signaling pathway. Targeting the PGE2/EP1/β1 integrin signaling pathway may aid in the development of new therapeutic strategies for the prevention and treatment of this type of cancer.
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Bai
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Qinyi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Periodontal, Institute of Stomatology, The Stomatological Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shu
authors.affiliation: Department of Pathology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shukai
authors.initials: S
authors.lastname: Xia
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shanyu
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yipin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Leng
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015232:Dinoprostone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019012:Integrin beta1; D016328:NF-kappa B; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone