Stimulation of urokinase-type plasminogen activator expression by blockage of E-cadherin-dependent cell-cell adhesion.
Decreased expression of the cell-cell adhesion molecule, E-cadherin, promotes dedifferentiation and invasiveness of human carcinoma cells, whereas this process can be reversed by reexpression of E-cadherin (U. H. Frixen et al., J. Cell Biol., 113: 173-185, 1991; J. H. Schipper et al., Cancer Res., 51: 6328-6337, 1991). In this work we studied the involvement of extracellular matrix-degrading proteases in E-cadherin-dependent tumor cell invasion. When T47D and MCF-7 human differentiated breast carcinoma cells were treated with the E-cadherin antibody DECMA (decompacting monoclonal antibody) the cells dissociated from each other and lost their epithelioid morphology, paralleled with a rise in the secretion of urokinase-type plasminogen activator (uPA) into the extracellular milieu as determined by zymography. The stimulation of uPA required protein and RNA synthesis. Furthermore, when DECMA-treated T47D cells were cultured on artificial collagen matrices the induced invasiveness correlated with accumulation of uPA in the culture medium, and uPA antibodies inhibited this invasion process. Actin filaments which are thought to be associated with the cytoplasmic part of E-cadherin were disrupted after treatment of T47D cells with DECMA. These results suggest a link between cell-cell adhesion, the integrity of actin filaments, and the regulation of uPA biosynthesis.
Frixen
U H
UH
Friedrich Miescher-Institut, Basel, Switzerland.
Nagamine
Y
Y
D000199:Actins / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D001943:Breast Neoplasms / Q000473:pathology; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion; D005260:Female; D006801:Humans; D008970:Molecular Weight; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D000199:Actins; D000911:Antibodies, Monoclonal; D015820:Cadherins; D014568:Urokinase-Type Plasminogen Activator