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

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_vβ ₆ extracted from histological sections. α_vβ ₆ 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_vβ ₆ 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.