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

作者：Huang, Chongbiao; Li, Na; Li, Zengxun; Chang, Antao; Chen, Yanan; Zhao, Tiansuo; Li, Yang; Wang, Xiuchao; Zhang, Wei; Wang, Zhimin; Luo, Lin; Shi, Jingjing; Yang, Shengyu; Ren, He^*; Hao, Jihui^*

来源：Nature Communications, 2017, 8(1): 14035.

DOI：10.1038/ncomms14035

• TRANSCELLULAR MIGRATION
• VASCULAR ENDOTHELIUM
• IL-35
• GROWTH
• GENE
• TARGET
• IDENTIFICATION
• SUPPRESSION
• INDUCTION
• CYTOKINE

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.

• 出版日期2017-1-19
• 单位天津医科大学; 南开大学