Characterization of integrin chains in normal and neoplastic human pancreas

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Abstract
Integrins are a complex family of non-covalently linked heterodimeric glycoproteins which function as cell adhesion molecules, interacting with extracellular matrix molecules such as laminin, fibronectin, vitronectin, and collagen, and also having a role in intercellular adhesion. Each integrin subfamily is characterized by a common β chain associated with variable α chains. We have examined, using immunohistological methods, the expression of the VLA (very late activation) family comprising β1 in association with α1–6, and also α6 in association with β4, the LFA β chain β2, and the vitronectin receptor, in association with β1 or β5 and as the complex αvβ3. Cryostat sections of normal pancreas, pancreatic adenocarcinomas, and ampullary tumours were studied together with six pancreatic carcinoma cell lines. Normal pancreas showed expression of β1 in all parenchyma. α2 and α6 had a similar distribution whereas α3 expression was confined to ducts, including the very smallest radicles. Staining along the basement membrances of ducts was seen with β4 and the anti-vitronection αv chain receptor antibody 13C2. Islet cells failed to stain with any antibody. No staining of epithelial components was seen with antibodies to α1, α4, α5, or to the αvβ3 form of the vitronectin receptor (β3 and αvβ3 using the antibody 23C6). Pancreatic adenocarcinomas and ampullary tumours showed expression of α2, α3, α6, β1, β4, and the vitronectin receptor (αv associated with β1 or β5). Well differentiated cell lines (BXPC-3 and Capan-2) showed an identical phenotype, but less well differentiated lines showed varible loss of one or more integrin chains. The functional role of integrins was quantitated by adhesion assays in which we could assess the ability of pancreatic carcinoma cells to stick to the extracellular matrix substrates fibronectin collagen, and laminin but not to fibrinogen or BSA. Binding of well differentiated cell lines to fibronectin and collagen was, in part, inhibited by exogenous RGD peptide. The distribution of integrins in normal and neoplastic cells and their functional properties were also shown to correlate well with the spatial distribution of laminin, fibronectin, and type IV collagen as shown by immunohistology in normal and neoplastic pancreas.