Y. Kikkawa et al., Integrin binding specificity of laminin-10/11 : laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrins, J CELL SCI, 113(5), 2000, pp. 869-876
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 we
re 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 invo
lved 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 inhibit
ed the adhesion of all cell types tested, anti-alpha 3 antibody inhibited t
he adhesion of carcinoma and glioma cells but not fibroblastic cells. Adhes
ion 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 an
d alpha 6 beta 1 integrins function as laminin-10/11 receptors in these cel
ls. 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 1 and alpha 6 beta 1 transfectants, whereas laminin-5
was the preferred ligand for the alpha 3 beta 1 transfectants. Upon stimul
ation with the activating antiintegrin beta 1 antibody, both transfectants
became more adherent to the substratum regardless of the type of laminins c
oated, although their preference for laminin isoforms remained unaltered. K
562 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 anot
her receptor for laminin-10/11. Even with lung carcinoma cells, the alpha 6
-containing integrins partly contributed to adhesion to laminin-10/11 at hi
gher coating concentrations, although non-integrin receptor(s) might also b
e involved under such conditions. These results indicated that laminin-10/1
1 are potent and versatile adhesive ligands in basement membranes capable o
f binding to both alpha 3 beta 1 and alpha 6 beta 1 integrins with high avi
dity and also to alpha 6 beta 4 integrin.