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

<jats:p><jats:bold>Aims</jats:bold> : To analyse the expression of α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub>, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types.</jats:p><jats:p><jats:bold>Methods and results</jats:bold> : A new monoclonal antibody to the human β<jats:sub>6</jats:sub> subunit, 5C4, was used to locate α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> extracted from histological sections. α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> 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<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well‐differentiated carcinomas expressed more β<jats:sub>6</jats:sub> than poorly differentiated tumours. Peritumoral epithelial tissues where α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub>‐expressing tumours arose also expressed α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub>. There was no correlation between expression of α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> up‐regulation, but appeared independent of classical ligand binding to α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub>.</jats:p><jats:p><jats:bold>Conclusions</jats:bold> : Our findings indicate that: (i) α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> is overexpressed in pancreatic adenocarcinomas; (ii) α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub>‐positive carcinomas originate from α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub>‐expressing tissues; (iii) α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) <jats:italic>in‐vitro</jats:italic> overexpression of α<jats:sub>v</jats:sub>β<jats:sub>6</jats:sub> in pancreatic carcinoma cell lines accompanies spheroid formation.</jats:p>