Expression and function of VLA‐α2, ‐α3, ‐α5 and ‐α6‐integrin receptors in pancreatic carcinoma

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Abstract
The expression of the VLA‐integrins α2, α3, v5 and α6 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 α2, α3, α5 and α6in pancreatic cancer cells. Immunohistochemically, VLA α2 and VLA α6 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 α3 and VLA α5. Pancreatic carcinoma showed intense staining for VLA α2 and VLA α6 with a diffuse distribution on the cell surface. The redistribution of VLA α2 and VLA α6 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 α3 and VLA α5 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 α2 (Gl 9, 10‐G‐11) were able to inhibit tumor‐cell adhesion to collagen IV (59%‐72%) in both cell lines. A MAb against α6 (GoH3) inhibited tumor‐cell adhesion to laminin (52%‐86%) in both cell lines. These results suggest that α2 is a collagen‐binding site and α6 a laminin‐binding site in pancreatic cancer cells. The anti‐α5‐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, α5is a functionally important fibronectin binding site in some pancreatic carcinoma cells, suggesting further RGD‐dependent fibronectin binding sites in other pancreatic carcinoma cells.

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