Laminin-10/11, the
laminin isoforms containing the alpha 5 chain, are major components of basement membranes of many fetal and adult tissues.
Laminin-10/11 purified from the
conditioned medium of human lung
carcinoma cells were potent in mediating adhesion of the
carcinoma cells in an
integrin alpha 3 beta 1-dependent manner. To further define the type(s) of
integrins involved in cell adhesion to
laminin-10/11, we examined the effects of a panel of function-blocking anti-
integrin antibodies on the adhesion of different cell types to
laminin-10/11. Although anti-
integrin beta 1 antibody inhibited the adhesion of all cell types tested, anti-alpha 3 antibody inhibited the adhesion of
carcinoma and
glioma cells but not fibroblastic cells. Adhesion of fibroblastic cells was inhibited, however, by a combination of anti-alpha 3 and anti-alpha 6
antibodies, suggesting that both alpha 3 beta 1 and alpha 6 beta 1
integrins function as
laminin-10/11 receptors in these cells. To explore this possibility, we examined the adhesion of K562 leukemic cells transfected with
integrin alpha 3 or alpha 6 subunit to
laminin-10/11 or other
laminin isoforms.
Laminin-10/11 were potent adhesive
ligands for both the alpha 3 beta 11 and alpha 6 beta 1 transfectants, whereas
laminin-5 was the preferred
ligand for the alpha 3 beta 1 transfectants. Upon stimulation with the activating anti-
integrin beta 1 antibody, both transfectants became more adherent to the substratum regardless of the type of laminins coated, although their preference for
laminin isoforms remained unaltered. K562 cells transfected with alpha 6 and beta 4 subunits were also capable of adhering to
laminin-10/11, indicating that
integrin alpha 6 beta 4 is another receptor for
laminin-10/11. Even with lung
carcinoma cells, the alpha 6-containing
integrins partly contributed to adhesion to
laminin-10/11 at higher coating concentrations, although non-
integrin receptor(s) might also be involved under such conditions. These results indicated that
laminin-10/11 are potent and versatile adhesive
ligands in basement membranes capable of binding to both alpha 3 beta 1 and alpha 6 beta 1
integrins with high avidity and also to
alpha 6 beta 4 integrin.