Expression and function of VLA‐α 2 , ‐α 3 , ‐α 5 and ‐α 6 ‐integrin receptors in pancreatic carcinoma

The expression of the VLA‐integrins α 2 , α 3 , v 5 and α 6 was studied immunohistochemically in tissue samples from ductal pancreatic cancer, chronic pancreatitis, normal pancreas and in 8 cell lines of ductal human pancreatic cancer. Furthermore, adhesion assays on purified extracellular matrix (ECM)‐compounds were used to define the function of α 2 , α 3 , α 5 and α 6 in pancreatic cancer cells. Immunohistochemically, VLA α 2 and VLA α 6 were moderately to strongly expressed on the basal surface of ductal and acinar cells in normal pancreatic tissue, while centro‐acinar cells predominantly expressed VLA α 3 and VLA α 5 . Pancreatic carcinoma showed intense staining for VLA α 2 and VLA α 6 with a diffuse distribution on the cell surface. The redistribution of VLA α 2 and VLA α 6 may reflect a loss of spatial arrangement of tumor cells and their ability to interact randomly with extracellular matrix structures during invasion and metastasis. Expression of VLA α 3 and VLA α 5 in pancreatic carcinoma was heterogeneous, ranging from moderate to weak, and was lost in about 50% of the cells. Two pancreatic carcinoma cell lines (PC 3, PC 44) were further investigated in adhesion assays. Monoclonal antibodies (MAbs) against α 2 (Gl 9, 10‐G‐11) were able to inhibit tumor‐cell adhesion to collagen IV (59%‐72%) in both cell lines. A MAb against α 6 (GoH 3 ) inhibited tumor‐cell adhesion to laminin (52%‐86%) in both cell lines. These results suggest that α 2 is a collagen‐binding site and α 6 a laminin‐binding site in pancreatic cancer cells. The anti‐α 5 ‐MAb SAM I inhibited adhesion of PC3 to fibronectin (76%), being without effect in PC44. Adhesion of both cell lines to fibronectin was almost completely inhibited by RGDS (85%‐88%). Thus, α 5 is a functionally important fibronectin binding site in some pancreatic carcinoma cells, suggesting further RGD‐dependent fibronectin binding sites in other pancreatic carcinoma cells. © 1992 Wiley‐Liss, Inc.