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; Jihui Hao

doi:10.1038/ncomms14035

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, Jihui Hao

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92 Scopus citations

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.

Original language	English (US)
Article number	14035
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14035
State	Published - 2017

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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@article{32a2e807e26f47f79680f8eaf9bbe33d,

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.",

author = "Chongbiao Huang and Na Li and Zengxun Li and Antao Chang and Yanan Chen and Tiansuo Zhao and Yang Li and Xiuchao Wang and Wei Zhang and Zhimin Wang and Lin Luo and Jingjing Shi and Shengyu Yang and He Ren and Jihui Hao",

note = "Funding Information: This work was supported by the National Natural Science Foundation of China (grants 81525021, 81502067, 81302082, 81272685, 31301151, 81172355, 31471340, 31470957, 81472264, 81401957 and 81602017), the Natural Science Foundation of Tianjin (grants 11JCZDJC18400, 13YCYBYC37400 and 16JCQNJC09900) and the Major Anticancer Technologies R&D Program of Tianjin (grant 12ZCDZSY16700). S.Y. is supported by the NIH (grant R01CA175741). Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

doi = "10.1038/ncomms14035",

language = "English (US)",

volume = "8",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression

AU - Huang, Chongbiao

AU - Li, Na

AU - Li, Zengxun

AU - Chang, Antao

AU - Chen, Yanan

AU - Zhao, Tiansuo

AU - Li, Yang

AU - Wang, Xiuchao

AU - Zhang, Wei

AU - Wang, Zhimin

AU - Luo, Lin

AU - Shi, Jingjing

AU - Yang, Shengyu

AU - Ren, He

AU - Hao, Jihui

N1 - Funding Information: This work was supported by the National Natural Science Foundation of China (grants 81525021, 81502067, 81302082, 81272685, 31301151, 81172355, 31471340, 31470957, 81472264, 81401957 and 81602017), the Natural Science Foundation of Tianjin (grants 11JCZDJC18400, 13YCYBYC37400 and 16JCQNJC09900) and the Major Anticancer Technologies R&D Program of Tianjin (grant 12ZCDZSY16700). S.Y. is supported by the NIH (grant R01CA175741). Publisher Copyright: © The Author(s) 2017.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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U2 - 10.1038/ncomms14035

DO - 10.1038/ncomms14035

M3 - Article

C2 - 28102193

AN - SCOPUS:85020903746

SN - 2041-1723

VL - 8

JO - Nature communications

JF - Nature communications

M1 - 14035

ER -

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

Abstract

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