The role of polymeric immunoglobulin receptor in inflammation-induced tumor metastasis of human hepatocellular carcinoma.
The role of polymeric immunoglobulin receptor in inflammation-induced tumor metastasis of human hepatocellular carcinoma.
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聚合免疫球蛋白受体在人肝细胞癌炎症诱导的肿瘤转移中的作用。
DOI：
10.1093/jnci/djr360
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发表时间：
2011-11-16
期刊：
影响因子：
--
通讯作者：
Geng M
中科院分区：
文献类型：
--
作者：
Ai J;Tang Q;Wu Y;Xu Y;Feng T;Zhou R;Chen Y;Gao X;Zhu Q;Yue X;Pan Q;Xu S;Li J;Huang M;Daugherty-Holtrop J;He Y;Xu HE;Fan J;Ding J;Geng M
聚合免疫球蛋白受体(PIgR)是聚合免疫球蛋白A和免疫球蛋白M的转运体，通常在病毒或细菌感染时表达增加，将先天免疫和获得性免疫联系起来。PIgR在肿瘤中的异常表达也被观察到，但其临床相关性仍不确定。应用人肝细胞癌组织芯片(n=254)研究pIgR表达与早期复发的关系。用严重联合免疫缺陷小鼠建立实验性肺转移模型，比较高表达pIgR的犬肾细胞(n=5只/组)和SMMC-7721(n=12只/组)细胞与对照细胞的转移潜能。采用RNA干扰、免疫沉淀和免疫印迹等方法研究pIgR在诱导上皮-间充质转化(EMT)中的作用。体外研究(免疫共沉淀、免疫印迹、迁移、侵袭和黏附实验)被用来确定pIgR介导的转移的机制。所有的统计检验都是双面的。在早期肝细胞癌和乙肝表面抗原阳性的肝细胞癌患者中，pIgR高表达与早期复发有统计学意义(LOG-RANK P=0.02)。注射pIgR过表达细胞的小鼠肺转移数显著高于相应的对照细胞(Madin-Darby犬肾细胞：pIgR平均值=29.4个肺转移结节与对照组相比，平均值=0.0个肺转移结节，差值=29.4个肺转移结节，95%可信区间=13.0~45.8，P=.001；SMMC-7721细胞：pIgR平均值=10.4个/肺转移结节，对照组平均=2.2个/肺转移结节，差值=8.2个/肺转移结节，95%可信区间=1.0~15.5，P=0.03)。此外，pIgR的高表达足以通过激活Smad信号诱导EMT。PIgR在EMT的诱导中起一定作用。我们的结果证实pIgR是乙肝病毒源性肝炎和肝细胞癌转移之间的潜在联系，并为pIgR作为肝细胞癌预后生物标志物和潜在治疗靶点提供证据。
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. 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. 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. 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.
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影响因子：
50.3
作者：
Ansieau, Stephane;Bastid, Jeremy;Puisieux, Alain
通讯作者：
Puisieux, Alain
DOI：
10.1056/nejmoa0804525
发表时间：
2008-11-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hoshida Y;Villanueva A;Kobayashi M;Peix J;Chiang DY;Camargo A;Gupta S;Moore J;Wrobel MJ;Lerner J;Reich M;Chan JA;Glickman JN;Ikeda K;Hashimoto M;Watanabe G;Daidone MG;Roayaie S;Schwartz M;Thung S;Salvesen HB;Gabriel S;Mazzaferro V;Bruix J;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
56.9
作者：
CASANOVA, JE;BREITFELD, PP;MOSTOV, KE
通讯作者：
MOSTOV, KE
影响因子：
3.4
作者：
ISAACSON, P
通讯作者：
ISAACSON, P
影响因子：
50.3
作者：
Huesemann, Yves;Geigl, Jochen B.;Klein, Christoph A.
通讯作者：
Klein, Christoph A.