DIFFERENTIAL MOTILE RESPONSE OF HUMAN-MALIGNANT MESOTHELIOMA CELLS TOFIBRONECTIN, LAMININ AND COLLAGEN TYPE-IV - THE ROLE OF BETA(1) INTEGRINS

beta(1) integrins are widely expressed in human tissues but their pres ence and function on malignant mesothelioma cells have not been examin ed. In this study, we have investigated the expression and function of beta(1) integrins in 7 human malignant mesothelioma cell lines, Immun ofluorescence staining and FAGS analysis showed similar expression of beta(1) integrins with strongest expression of alpha(3) beta(1) in all investigated mesothelioma cell lines, Using the Boyden chamber assay, we found that mesothelioma cell lines migrated to soluble (chemotaxis ) and substrate-bound (haptotaxis) fibronectin, laminin and collagen t ype IV, In order to investigate the biological function of integrins i n mesothelioma cells, we pre-incubated the cells with blocking anti-in tegrin monoclonal antibodies (MAbs) prior to the adhesion and migratio n assays. Anti-beta(1) antibodies inhibited cell adhesion, chemotaxis and haptotaxis in all cell lines. Generally, anti-alpha(2) integrin an tibodies inhibited cell adhesion, chemotactic and haptotactic migratio n to collagen type IV, whereas antibodies to the alpha(5) and alpha(6) subunits inhibited cell adhesion and migration to fibronectin and lam inin, respectively. Preincubation of mesothelioma cells with anti-alph a(3) antibodies inhibited the migration to either collagen type IV, la minin or fibronectin in all cell lines, Interestingly, in 3 cell lines anti-alpha(3) antibodies inhibited cell migration to laminin and coll agen type IV without affecting the ability of the cells to adhere to t hese proteins. Furthermore, in 2 cell lines, antibodies to the alpha(3 ) chain inhibited chemotaxis but not haptotaxis to collagen type IV, i ndicating the presence of distinct signalling pathways. (C) 1997 Wiley -Liss, Inc.