Activation of beta1 integrins induces cell-cell adhesion.
Integrins are highly regulated receptors that can function in both cell-substrate and cell-cell adhesion. We have found that the activating anti-beta1 mAb, 12G10, can specifically and rapidly induce both cell-substrate and cell-cell adhesion of HT-1080 human fibrosarcoma and other cell types. Binding of mAb 12G10 induced clustering of cell-surface integrins, and the preferential localization of beta1 integrins expressing the 12G10 epitope at cell-cell adhesion sites. Fab fragments of mAb 12G10 induced HT-1080 cell-cell adhesion as effectively as did intact antibodies, suggesting that integrin clustering was not due to direct antibody crosslinking. Latrunculin B, an inhibitor of F-actin polymerization, inhibited cell-cell adhesion but not the clustering of integrins. Results from a novel, two-color cell-cell adhesion assay suggested that nonactivated cells can bind to activated cells and that integrin activation-induced HT-1080 cell-cell adhesion minimally requires the interaction of activated alpha2beta1 with nonactivated alpha3beta1. These findings suggest that HT-1080 cell-cell adhesion induced by integrin activation require a signaling process involving integrin clustering and the subsequent organization of the cytoskeleton. Integrin activation could therefore play a key role in cell-cell adhesion.
Whittard
J D
JD
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Akiyama
S K
SK
D000199:Actins / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005353:Fibronectins / Q000378:metabolism; D005354:Fibrosarcoma; D006801:Humans; D006825:Hybridomas; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014407:Tumor Cells, Cultured
D000199:Actins; D000911:Antibodies, Monoclonal; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015820:Cadherins; D002413:Cations, Divalent; D000939:Epitopes; D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin; D013844:Thiazoles; D053778:Thiazolidines; D003094:Collagen; C037068:latrunculin B