Cell-cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells.
L-cells were cotransfected with plasmids coding for mouse E-cadherin (uvomorulin) and the neophosphotransferase gene, and stable transfectants expressing E-cadherin at the cell surface were selected and cloned. Control transfection was done with the neophosphotransferase gene alone. The invasive migration of transfected and untransfected L-cells into three-dimensional collagen gels was then analyzed. L-cells not expressing E-cadherin migrated efficiently into the gels, whereas invasion of the E-cadherin-expressing L-cells was restricted in a cell density dependent manner. At sparse density, when the cells exhibited little cell-cell contacts, no difference was observed between the level of invasion of the cadherin-expressing cells and the control cells. However, with increasing cell density, decreasing amounts of the cadherin-expressing cells but increasing amounts of the control cells migrated into the gels. At confluent density hardly any cadherin-expressing cells were able to migrate into the gels. The inhibition of the invasion of the cadherin-expressing cells could be reverted if confluent cells were cultured in the presence of monoclonal antibodies against E-cadherin. Since the expression of E-cadherin did not influence the invasive mobility of single cells, these results indicate that E-cadherin-mediated cell-cell contacts inhibited invasive cellular migration. Time-lapse videoscopy and studies of cell migration from a monolayer into a cell-free area demonstrated that the restricted invasion could be explained by contact inhibition of cell movement of the cadherin-expressing cells.
Chen
W C
WC
Department of Medical Cell Biology, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden.
Obrink
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015820:Cadherins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002452:Cell Count / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003094:Collagen; D005109:Extracellular Matrix / Q000378:metabolism; D005782:Gels; D006801:Humans; D007739:L Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010770:Phosphotransferases / Q000235:genetics; D010957:Plasmids; D014162:Transfection
D000911:Antibodies, Monoclonal; D015820:Cadherins; D015815:Cell Adhesion Molecules; D005782:Gels; D003094:Collagen; D010770:Phosphotransferases