THE INTEGRIN ALPHA-6-BETA-4 IS A LAMININ RECEPTOR

In this study, the putative laminin receptor function of the alpha-6-beta-4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha-6-beta-4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, an alpha-6 specific antibody (60% inhibition), as well as by A9, a beta-4 specific antibody (30% inhibition). Most importantly, we demonstrate that alpha-6-beta-4 binds specifically to laminin-Sepharose columns in the presence of either Mg2+ or Mn2+ and it is eluted from these columns with EDTA but not with NaCl. The alpha-6-beta-4 integrin does not bind to collagen-Sepharose, but the alpha-2-beta-1 integrin does bind. Clone A cells do not express alpha-6-alpha-1 as evidenced by the following observations: (a) no beta-1-integrin is detected in beta-1 immunoblots of GoH3 immunoprecipitates; and (b) no alpha-6-beta-1 integrin is seen in GoH3 immunoprecipitates of clone A extracts that had been immunodepleted of all beta-4 containing integrin using the A9 antibody. These data establish that laminin is a ligand for the alpha-6-beta-1 integrin and that this integrin can function as a laminin receptor independently of alpha-6-beta-1.