High expression of Claudin-2 in esophageal carcinoma and precancerous lesions is significantly associated with the bile salt receptors VDR and TGR5

BMC Gastroenterology

Research Article

Amy Lalonde¹  Tongtong Wu¹  Jun Sun²  Zhongren Zhou³  Sohaib Abu-Farsakh³ 

[1] Department of Biostatistics and Computational Biology, University of Rochester Medical Center, 265 Crittenden Boulevard CU 420630, 14642-0630, Rochester, NY, USA;Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois College of Medicine, 840 South Wood Street MC 716, 60612, Chicago, IL, USA;Department of Pathology and Laboratory Medicine, University of Rochester, Box 626, 601 Elmwood Ave, 14642, Rochester, NY, USA;

关键词: Claudin 2;    Esophageal adenocarcinoma;    Barrett’s esophagus;    Tight junctions;    VDR;    TGR5;   

DOI  :  10.1186/s12876-017-0590-0

 received in 2016-08-02, accepted in 2017-02-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundClaudins are a family of integral membrane proteins and are components of tight junctions (TJs). Many TJ proteins are known to tighten the cell structure and maintain a barrier. Claudin-2 forms gated paracellular channels and allows sodium ions and other small positively charged ions to cross between adjacent cells. Recently, we found that vitamin D receptor (VDR) enhanced Claudin-2 expression in colon and that bile salt receptors VDR and Takeda G-protein coupled receptor5 (TGR5) were highly expressed in esophageal adenocarcinoma (EAC) and precancerous lesions. Here, we examined the expression of Claudin-2 in EAC and precancerous lesions and its association with VDR and TGR5 expression.MethodsClaudin-2 expression was examined by immunohistochemistry on tissue microarrays, containing EAC, high grade dysplasia (HGD), low grade dysplasia (LGD), Barrett’s esophagus (BE), columnar cell metaplasia (CM), squamous cell carcinoma (SCC), and squamous epithelium (SE) cases. Intensity (0 to 3) and percentage were scored for each case. High expression was defined as 2–3 intensity in ≥ 10% of cells.ResultsClaudin-2 was highly expressed in 77% EAC (86/111), 38% HGD (5/13), 61% LGD (17/28), 46% BE (18/39), 45% CM (29/65), 88% SCC (23/26), and 14% SE (11/76). It was significantly more highly-expressed in EAC, SCC and glandular lesions than in SE and more in EAC than in BE and CM. A significant association was found between Claudin-2 expression and VDR and TGR5 expression. No significant association was found between expression of Claudin-2 and age, gender, grade, stage, or patients’ survival time in EAC and SCC.ConclusionsWe conclude that Claudin-2 expression is significantly associated with bile acid receptors VDR and TGR5 expression. Our studies identify a novel role of a tight junction protein in the development and progression of esophageal mucosal metaplasia, dysplasia and carcinoma.

【 授权许可】

CC BY   
© The Author(s). 2017