Immunohistochemical screening for β6‐integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up‐regulation in pancreatic ductal adenocarcinomas in vivo and in vitro

Abstract

Aims : To analyse the expression of α_vβ₆, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types. Methods and results : A new monoclonal antibody to the human β₆ subunit, 5C4, was used to locate α_vβ₆ in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of α_vβ₆ extracted from histological sections. α_vβ₆ integrin showed strongest expression in 34 pancreatic ductal adenocarcinomas (mean score 2.88 ± 0.52), followed by 24 intestinal‐type gastric carcinomas (1.45 ± 1.06) and eight lung adenocarcinomas (1.37 ± 1.1). Moderate expression was found in 31 diffuse‐type gastric carcinomas (0.94 ± 0.83), seven duodenal adenocarcinomas (0.8 ± 1.34) and 26 colorectal adenocarcinomas (0.76 ± 0.71). Little α_vβ₆ was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well‐differentiated carcinomas expressed more β₆ than poorly differentiated tumours. Peritumoral epithelial tissues where α_vβ₆‐expressing tumours arose also expressed α_vβ₆. There was no correlation between expression of α_vβ₆ and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to α_vβ₆ up‐regulation, but appeared independent of classical ligand binding to α_vβ₆. Conclusions : Our findings indicate that: (i) α_vβ₆ is overexpressed in pancreatic adenocarcinomas; (ii) α_vβ₆‐positive carcinomas originate from α_vβ₆‐expressing tissues; (iii) α_vβ₆ expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in‐vitro overexpression of α_vβ₆ in pancreatic carcinoma cell lines accompanies spheroid formation.