Expression of polymeric immunoglobulin receptor and stromal activity in pancreatic ductal adenocarcinoma
Expression of polymeric immunoglobulin receptor and stromal activity in pancreatic ductal adenocarcinoma
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DOI：
10.1016/j.pan.2017.01.013
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发表时间：
2017-03-01
期刊：
影响因子：
3.6
通讯作者：
Kocher, Hemant M.
中科院分区：
文献类型：
--
作者：
Arumugam, Prabhu;Bhattacharya, Satyajit;Kocher, Hemant M.
背景/目标：聚合免疫球蛋白受体 (pIgR) 通过正常粘膜的上皮细胞运输免疫球蛋白（IgA 和 IgM），但在正常胰腺中均不表达。我们实验室最近的研究表明 pIgR 在胰腺导管腺癌 (PDAC) 中可能上调。我们的目的是评估 pIgR 在人类 PDAC 中的作用。方法：在细胞系中操纵 pIgR 表达（siRNA 和 shRNA），以评估其对 2D 测定以及 3D 器官型模型中细胞行为的后续影响。在 pIgR、α SMA、E-钙粘蛋白和天狼星红染色后，对 88 名 PDAC 患者的组织微阵列进行了分析，以评估其作为组合生物标志物组的作用。结果：白细胞介素 4 (IL4) 和肿瘤坏死因子 (TNF α) 等细胞因子无法调节 PDAC 细胞系中的 pIgR 表达，尽管在其他研究中也发现了这种效应。 Capan1 癌细胞系中 pIgR 表达的下调导致 2D 检测中细胞增殖、粘附和迁移的减少。在 3D 拟体器官模型中，pIgR 下调导致癌细胞侵袭减少、顶端基底极性改变和基质活性减弱。在人 PDAC 中，E-钙粘蛋白表达减少与胰腺上皮内瘤变 (PanIN) 进展过程中 pIgR 表达增加相关。结合增强的基质指数（α-平滑肌作用（SMA）和天狼星红），低 pIgR 评分有改善生存的趋势。结论：pIgR 可能参与 PDAC 进展，并可能与基质活性有关。需要在体内模型中进一步研究其精确作用，以了解其对癌症进展的影响。 (C) 2017 年 IAP 和 EPC。由 Elsevier B.V. 出版。保留所有权利。
Background/objectives: Polymeric immunoglobulin receptor (pIgR) traffics Immunoglobulins (IgA and IgM) through epithelial cells in normal mucosae but neither are expressed in the normal pancreas. Recent work from our laboratory suggested pIgR may be upregulated in pancreatic ductal adenocarcinoma (PDAC). Our aim was to assess the role of pIgR in human PDAC.Methods: pIgR expression was manipulated (siRNA and shRNA) in cell lines to evaluate its subsequent effect on cell behaviour in 2D assays as well as 3D organotypics models. Tissue Microarrays of 88 patients with PDAC were analysed after pIgR, alpha SMA, E-Cadherin and Picrosirius Red staining to assess their role as a combined bio-marker panel.Results: Cytokines such as interleukin 4 (IL4) and Tumour Necrosis Factor (TNF alpha) could not modulate pIgR expression in PDAC cell lines despite this effect being seen in other studies. Down-regulation in pIgR expression in Capan1 cancer cell line resulted in reduction of cellular proliferation, adhesion and migration in 2D assays. In 3D physiomimetic organotypic models, pIgR downregulation resulted in reduced cancer cell invasion, alteration of apico-basal polarity and diminished stromal activity. In human PDAC, decreased E-cadherin expression correlates with increased pIgR expression through pancreatic intra-epithelial neoplasia (PanIN) progression. In combination with enhanced stromal indices (alpha-smooth muscle action (SMA) and Picrosirius red), low pIgR scores had a trend towards better survival.Conclusion: pIgR may be involved in PDAC progression and may be linked stromal activity. Further work on its precise role is mandated in in vivo models, to understand its influence on cancer progression. (C) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.