Expression of polymeric immunoglobulin receptor and stromal activity in pancreatic ductal adenocarcinoma.
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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, αSMA, 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 (TNFα) 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 (α-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.