Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression

Chongbiao Huang, Na Li, Zengxun Li, Antao Chang, Yanan Chen, Tiansuo Zhao, Yang Li, Xiuchao Wang, Wei Zhang, Zhimin Wang, Lin Luo, Jingjing Shi, Shengyu Yang, He Ren () and Jihui Hao ()
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Chongbiao Huang: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer
Na Li: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer
Zengxun Li: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer
Antao Chang: School of Medicine, Nankai University
Yanan Chen: School of Medicine, Nankai University
Tiansuo Zhao: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer
Yang Li: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer
Xiuchao Wang: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer
Wei Zhang: Tianjin Hepingqu Gynaechology and Obstetrics Hospital
Zhimin Wang: Tianjin Hepingqu Gynaechology and Obstetrics Hospital
Lin Luo: Tianjin Hepingqu Gynaechology and Obstetrics Hospital
Jingjing Shi: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy
Shengyu Yang: Penn State University College of Medicine
He Ren: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer
Jihui Hao: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14035

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