The Role of Polymeric Immunoglobulin Receptor in Inflammation-Induced Tumor Metastasis of Human Hepatocellular Carcinoma

被引：77

作者：

Ai, Jing ^{[1
]}

Tang, Qingjuan ^{[2
]}

Wu, Yanlin ^{[2
]}

Xu, Yang ^{[3
,4
,5
]}

Feng, Teng ^{[2
]}

Zhou, Ruiyu ^{[2
]}

Chen, Yi ^{[1
]}

Gao, Xin ^{[1
]}

Zhu, Qingfeng ^{[3
,4
,5
]}

Yue, Xihua ^{[1
]}

Pan, Qiuming ^{[1
]}

Xu, Siyun ^{[2
]}

Li, Jing ^{[2
]}

Huang, Min ^{[1
]}

Daugherty-Holtrop, Jennifer ^{[1
,6
]}

He, Yuanzheng ^{[6
]}

Xu, H. Eric ^{[6
,7
]}

Fan, Jia ^{[3
,4
,5
]}

Ding, Jian

Geng, Meiyu ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China

[2] Ocean Univ China, Sch Med & Pharm, Dept Pharmacol & Glycobiol, Qingdao 266003, Shandong, Peoples R China

[3] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg, Shanghai 200433, Peoples R China

[4] Fudan Univ, Shanghai Med Sch, Shanghai 200433, Peoples R China

[5] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China

[6] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI USA

[7] Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Struct Biol Drug Targets, Shanghai 201203, Peoples R China

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2011年 / 103卷 / 22期

基金：

中国国家自然科学基金;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; SECRETORY COMPONENT; BREAST-CANCER; TGF-BETA; PULMONARY ADENOCARCINOMA; GENE-EXPRESSION; CELLS; RESECTION; EMT; INTERNALIZATION;

D O I：

10.1093/jnci/djr360

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background Expression of the polymeric immunoglobulin receptor (pIgR), a transporter of polymeric IgA and IgM, is commonly increased in response to viral or bacterial infections, linking innate and adaptive immunity. Abnormal expression of pIgR in cancer was also observed, but its clinical relevance remains uncertain. Methods A human hepatocellular carcinoma (HCC) tissue microarray (n = 254) was used to investigate the association between pIgR expression and early recurrence. An experimental lung metastasis model using severe combined immune-deficient mice was applied to determine the metastatic potential of Madin-Darby canine kidney (n = 5 mice per group) and SMMC-7721 (n = 12 mice per group) cells overexpressing pIgR vs control cells. RNA interference, immunoprecipitation, and immunoblotting were performed to investigate the potential role for pIgR in the induction of epithelial-mesenchymal transition (EMT). In vitro studies (co-immunoprecipitation, immunoblotting, and migration, invasion, and adhesion assays) were used to determine the mechanisms behind pIgR-mediated metastasis. All statistical tests were two-sided. Results High expression of pIgR was statistically significantly associated with early recurrence in early-stage HCC and in hepatitis B surface antigen-positive HCC patients (log-rank P = .02). Mice injected with pIgR-overexpressing cells had a statistically significantly higher number of lung metastases compared with respective control cells (Madin-Darby canine kidney cells: pIgR mean = 29.4 metastatic nodules per lung vs control mean = 0.0 metastatic nodules per lung, difference = 29.4 metastatic nodules per lung, 95% confidence interval = 13.0 to 45.8, P = .001; SMMC-7721 cells: pIgR mean = 10.4 metastatic nodules per lung vs control mean = 2.2 metastatic nodules per lung, difference = 8.2 metastatic nodules per lung, 95% confidence interval = 1.0 to 15.5, P = .03). Furthermore, high expression of pIgR was sufficient to induce EMT through activation of Smad signaling. Conclusions pIgR plays a role in the induction of EMT. Our results identify pIgR as a potential link between hepatitis B virus-derived hepatitis and HCC metastasis and provide evidence in support of pIgR as a prognostic biomarker for HCC and a potential therapeutic target.

引用

页码：1696 / 1712

页数：17

共 66 条

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