The Role of Polymeric Immunoglobulin Receptor in Inflammation-Induced Tumor Metastasis of Human Hepatocellular Carcinoma
文献类型:期刊论文
作者 | Ai, Jing2![]() ![]() |
刊名 | JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
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出版日期 | 2011-11 |
卷号 | 103期号:22页码:1696-1712 |
ISSN号 | 0027-8874 |
DOI | 10.1093/jnci/djr360 |
文献子类 | Article |
英文摘要 | 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. |
WOS关键词 | EPITHELIAL-MESENCHYMAL TRANSITION ; SECRETORY COMPONENT ; BREAST-CANCER ; TGF-BETA ; PULMONARY ADENOCARCINOMA ; GENE-EXPRESSION ; CELLS ; RESECTION ; EMT ; INTERNALIZATION |
资助项目 | Natural Science Foundation of China[30725046] ; Natural Science Foundation of China[81021062] ; National Key Sci-Tech Special Project of Infectious Diseases[2008ZX10002-022] ; National Natural Science Foundation of China[30873039] |
WOS研究方向 | Oncology |
语种 | 英语 |
WOS记录号 | WOS:000297209000011 |
出版者 | OXFORD UNIV PRESS INC |
源URL | [http://119.78.100.183/handle/2S10ELR8/278352] ![]() |
专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
通讯作者 | Geng, Meiyu |
作者单位 | 1.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 3.Ocean Univ China, Sch Med & Pharm, Dept Pharmacol & Glycobiol, Qingdao 266003, Shandong, Peoples R China; 4.Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg, Shanghai 200433, Peoples R China; 5.Fudan Univ, Shanghai Med Sch, Shanghai 200433, Peoples R China; 6.Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China; 7.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Struct Biol Drug Targets, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Ai, Jing,Tang, Qingjuan,Wu, Yanlin,et al. The Role of Polymeric Immunoglobulin Receptor in Inflammation-Induced Tumor Metastasis of Human Hepatocellular Carcinoma[J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE,2011,103(22):1696-1712. |
APA | Ai, Jing.,Tang, Qingjuan.,Wu, Yanlin.,Xu, Yang.,Feng, Teng.,...&Geng, Meiyu.(2011).The Role of Polymeric Immunoglobulin Receptor in Inflammation-Induced Tumor Metastasis of Human Hepatocellular Carcinoma.JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE,103(22),1696-1712. |
MLA | Ai, Jing,et al."The Role of Polymeric Immunoglobulin Receptor in Inflammation-Induced Tumor Metastasis of Human Hepatocellular Carcinoma".JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 103.22(2011):1696-1712. |
入库方式: OAI收割
来源:上海药物研究所
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