beta 1 integrins play an essential role in adhesion and invasion of pancreatic carcinoma cells

To investigate the role of beta 1 integrins in pancreatic carcinoma invasio n, we analyzed the relationship between the activity of beta 1 integrins an d the invasive ability of human pancreatic carcinoma cell lines. AsPC1, BxP C3, PANC1, SU8686, KP1NL, KP2, and H48N cells had high expression of beta 1 and alpha 6 subunits, and various levels of alpha 2, alpha 3, and alpha 5 expression as determined by flow cytometry. Cell adhesion assay revealed th at alpha 2 beta 1, alpha 5 beta 1, and alpha 6 beta 1 integrins were the pr edominant adhesion receptors for collagen, fibronectin, and laminin, respec tively. beta 1 integrins on different cell types showed a wide range of con stitutive activity. Anti-beta 1 monoclonal antibody (MAB) TS2/16 rapidly ac tivated beta 1 integrins, and thus TS2/16 requirement in cell adhesion repr esented the levels of constitutive activity of beta 1 integrins. Notably, a s the result of in vitro chemoinvasion assay, the levels of constitutive ac tivity of beta 1 integrins correlated with the invasive ability of pancreat ic carcinoma cells. The inhibitory anti-beta 1 MAB 13 completely blocked th e invasion of these cell lines. Alternatively, the stimulatory anti-beta 1 MAB TS2/16 strongly inhibited the invasion. These results show an essential role of beta 1 integrins in invasion of pancreatic carcinoma cells and als o suggest subtle regulatory mechanisms of cell invasion.