The Integrin α6β4 Is a Laminin Receptor

In this study, the putative laminin receptor function of the α6β4 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 α6β4 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 α6 specific antibody (60% inhibition), as well as by A9, a β4 specific antibody (30% inhibition). Most importantly, we demonstrate that α6β4 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 α6β4 integrin does not bind to collagen-Sepharose, but the α2β1 integrin does bind. Clone A cells do not express α6β1 as evidenced by the following observations: (a) no β1 integrin is detected in β1 immunoblots of GoH3 immunoprecipitates; and (b) no α6β1 integrin is seen in GoH3 immunoprecipitates of clone A extracts that had been immunodepleted of all β4 containing integrin using the A9 antibody. These data establish that laminin is a ligand for the α6β4 integrin and that this integrin can function as a laminin receptor independently of α6β1.