Integrins are highly regulated receptors that can function in both cell-sub
strate and cell-cell adhesion. We have found that the activating anti-beta
(1) mAb, 12G10, can specifically and rapidly induce both cell-substrate and
cell-cell adhesion of HT-1080 human fibrosarcoma and other cell types. Bin
ding of mAb 12G10 induced clustering of cell-surface integrins, and the pre
ferential localization of beta (1) integrins expressing the 12G10 epitope a
t cell-cell adhesion sites, Fab fragments of mAb 12G10 induced HT-1080 cell
-cell adhesion as effectively as did intact antibodies, suggesting that int
egrin 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 cell
s and that integrin activation-induced MT-1080 cell-cell adhesion minimally
requires the interaction of activated alpha (2)beta (1) with nonactivated
alpha (3)beta (1). These findings suggest that MT-1080 cell-cell adhesion i
nduced by integrin activation require a signaling process involving integri
n clustering and the subsequent organization of the cytoskeleton, Integrin
activation could therefore play a key role in cell-cell adhesion.