Wu H.-H.Hwang-Verslues W.W.Lee W.-H.Huang C.-K.Wei P.-C.Chen C.-L.Shew J.-Y.Lee E.-Y.-H.P.YUNG-MING JENGYU-WEN TIENMa C.Lee W.-H.2020-03-062020-03-0620150022-1007https://www.scopus.com/inward/record.uri?eid=2-s2.0-84924700441&doi=10.1084%2fjem.20141702&partnerID=40&md5=c90590c01fea3919635dfd976461dacbhttps://scholars.lib.ntu.edu.tw/handle/123456789/473325Pancreatic cancer has an extremely high mortality rate due to its aggressive metastatic nature. Resolving the underlying mechanisms will be crucial for treatment. Here, we found that overexpression of IL-17B receptor (IL-17RB) strongly correlated with postoperative metastasis and inversely correlated with progression-free survival in pancreatic cancer patients. Consistently, results from ex vivo experiments further validated that IL-17RB and its ligand, IL-17B, plays an essential role in pancreatic cancer metastasis and malignancy. Signals from IL-17B-IL-17RB activated CCL20/CXCL1/IL-8/TFF1 chemokine expressions via the ERK1/2 pathway to promote cancer cell invasion, macrophage and endothelial cell recruitment at primary sites, and cancer cell survival at distant organs. Treatment with a newly derived monoclonal antibody against IL-17RB blocked tumor metastasis and promoted survival in a mouse xenograft model. These findings not only illustrate a key mechanism underlying the highly aggressive characteristics of pancreatic cancer but also provide a practical approach to tackle this disease. ? 2015 Wu et al.[SDGs]SDG3antineoplastic agent; CXCL1 chemokine; cytokine; interleukin 17B; interleukin 17B receptor; interleukin 17B receptor antibody; interleukin 8; macrophage inflammatory protein 3alpha; mitogen activated protein kinase; monoclonal antibody; unclassified drug; chemokine; interleukin 17; interleukin 17 receptor; monoclonal antibody; adult; animal experiment; animal model; antineoplastic activity; Article; cancer cell; cancer growth; cancer inhibition; cancer localization; cancer survival; cell invasion; drug targeting; endothelium cell; female; gene overexpression; human; macrophage; male; metastasis; mouse; nonhuman; pancreas cancer; priority journal; progression free survival; signal transduction; animal; disease free survival; drug screening; gene expression regulation; genetics; immunology; metabolism; middle aged; mortality; Pancreatic Neoplasms; pathology; SCID mouse; Animals; Antibodies, Monoclonal; Chemokines; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-17; Male; Mice, SCID; Middle Aged; Pancreatic Neoplasms; Receptors, Interleukin-17; Signal Transduction; Xenograft Model Antitumor Assaysjournal article10.1084/jem.20141702257323062-s2.0-84924700441