INTEGRIN ALPHA-6 EXPRESSION IN HUMAN PROSTATE CARCINOMA-CELLS IS ASSOCIATED WITH A MIGRATORY AND INVASIVE PHENOTYPE IN-VITRO AND IN-VIVO

Cell adhesion and migration are important features in tumor invasion, being mediated in part by integrins (extracellular matrix receptors), Integrins are significantly decreased in human prostate cancer. An exc eption is alpha 6 integrin (laminin receptor) which persists during pr ostate tumor progression, We have selected high (DU-H) and low (DU-L) expressors of alpha 6 integrin from a human prostate tumor cell line, DU145, to assess experimentally the importance of alpha 6 integrin in tumor invasion, DU-H cells exhibited a four-fold increased expression of alpha 6 integrin on the surface compared to DU-L cells, Both cell t ypes contained similar amounts of alpha 3 and alpha 5 integrin, The DU -H cells contained alpha 6 subunits complexed with both the beta 1 and beta 4 subunits whereas DU-L cells contained alpha 6 complexed only w ith beta 4, DU-H cells were three times more mobile on laminin as comp ared to DU-L, but adhered similarly on laminin, Adhesion and migration were inhibited with anti-alpha 6 antibody, Each subline was injected intraperitoneally into SCID mice to test its invasive potential, Resul ts showed greater invasion of DU-H compared to DU-L cells, with increa sed expression of alpha 6 integrin on the tumor at the areas of invasi on, These data suggest that alpha 6 integrin expression is advantageou s for prostate tumor cell invasion.