Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression.
Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression.
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肿瘤源性白细胞介素35通过诱导ICAM1表达促进胰腺导管腺癌细胞外渗和转移
DOI：
10.1038/ncomms14035
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发表时间：
2017-01-19
影响因子：
16.6
通讯作者：
Hao J
中科院分区：
文献类型：
--
作者：
Huang C;Li N;Li Z;Chang A;Chen Y;Zhao T;Li Y;Wang X;Zhang W;Wang Z;Luo L;Shi J;Yang S;Ren H;Hao J
白细胞介素35（IL-35）是IL-12家族的新成员，由EB病毒诱导基因3（EBI 3）亚基和P35亚基组成。IL-35是主要由调节性T细胞产生的免疫抑制性细胞因子。然而，IL-35在癌症转移和进展中的作用还不清楚。在这里，我们证明了IL-35在人胰腺导管腺癌（PDAC）组织中过表达，并且IL-35过表达与PDAC患者的不良预后相关。IL-35通过促进与内皮细胞的粘附和跨内皮外渗在PDAC细胞外渗和转移中起关键作用。IL-35通过GP 130-STAT 1信号通路促进ICAM 1的过度表达，从而通过ICAM 1-纤维蛋白原-ICAM 1桥促进内皮细胞粘附和跨内皮细胞迁移。在原位异种移植模型中，IL-35以ICAM 1依赖性方式促进自发性胰腺癌转移。总之，我们的研究结果表明IL-35通过介导ICAM 1的表达在促进PDAC转移中具有额外的功能。
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 promotesICAM1overexpression 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 anICAM1-dependent manner. Together, our results indicate additional functions of IL-35 in promoting PDAC metastasis through mediatingICAM1expression.
影响因子：
3.7
作者：
Djafarzadeh R;Sauter M;Notohamiprodjo S;Noessner E;Goyal P;Siess W;Wörnle M;Ribeiro A;Himmelein S;Sitter T;Nelson PJ
通讯作者：
Nelson PJ