??1 Integrins Play an Essential Role in Adhesion and Invasion of Pancreatic Carcinoma Cells

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Abstract
To investigate the role of β1 integrins in pancreatic carcinoma invasion, we analyzed the relationship between the activity of β1 integrins and the invasive ability of human pancreatic carcinoma cell lines. AsPC1, BxPC3, PANC1, SU8686, KP1NL, KP2, and H48N cells had high expression of β1 and α6 subunits, and various levels of α2, α3, and α5 expression as determined by flow cytometry. Cell adhesion assay revealed that α2β1, α5β1, and α6β1 integrins were the predominant adhesion receptors for collagen, fibronectin, and laminin, respectively. β1 integrins on different cell types showed a wide range of constitutive activity. Anti-β1 monoclonal antibody (MAB) TS2/16 rapidly activated β1 integrins, and thus TS2/16 requirement in cell adhesion represented the levels of constitutive activity of β1 integrins. Notably, as the result of in vitro chemoinvasion assay, the levels of constitutive activity of β1 integrins correlated with the invasive ability of pancreatic carcinoma cells. The inhibitory anti-β1 MAB 13 completely blocked the invasion of these cell lines. Alternatively, the stimulatory anti-β1 MAB TS2/16 strongly inhibited the invasion. These results show an essential role of β1 integrins in invasion of pancreatic carcinoma cells and also suggest subtle regulatory mechanisms of cell invasion.

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