title: Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression.
abstract: Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation. Mechanistically, IL-35 promotes ICAM1 overexpression through a GP130-STAT1 signalling pathway, which facilitates endothelial adhesion and transendothelial migration via an ICAM1-fibrinogen-ICAM1 bridge. In an orthotopic xenograft model, IL-35 promotes spontaneous pancreatic cancer metastasis in an ICAM1-dependent manner. Together, our results indicate additional functions of IL-35 in promoting PDAC metastasis through mediating ICAM1 expression.
authors.affiliation: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.|Senior Ward, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Chongbiao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Zengxun
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Antao
authors.initials: A
authors.lastname: Chang
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Tiansuo
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Xiuchao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tianjin Hepingqu Gynaechology and Obstetrics Hospital, Tianjin 300000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Tianjin Hepingqu Gynaechology and Obstetrics Hospital, Tianjin 300000, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Tianjin Hepingqu Gynaechology and Obstetrics Hospital, Tianjin 300000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Tissue Bank, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: Shengyu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: He
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Hao
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C573420:ICAM1 protein, human; C090509:Icam1 protein, mouse; D007378:Interleukins; C532417:interleukin-35, human; C569375:interleukin-35, mouse; D018799:Intercellular Adhesion Molecule-1