title: 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.
abstract: 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.
authors.affiliation: Research Institute, Osaka Medical Center for Maternal and Child Health, Izumi, Osaka 594-1101, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: N
authors.initials: N
authors.lastname: Sanzen
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
authors.forename: A
authors.initials: A
authors.lastname: Sonnenberg
authors.forename: K
authors.initials: K
authors.lastname: Sekiguchi
mesh_terms: D015703:Antigens, CD / Q000502:physiology; D000954:Antigens, Surface / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D039201:Integrin alpha3beta1; D039503:Integrin alpha6; D039121:Integrin alpha6beta1; D039161:Integrin alpha6beta4; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020014:K562 Cells; D007797:Laminin / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D039201:Integrin alpha3beta1; D039503:Integrin alpha6; D039121:Integrin alpha6beta1; D039161:Integrin alpha6beta4; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D020033:Protein Isoforms; D017474:Receptors, Laminin; C119013:laminin 10