Abstract. 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, decreasxE formation and maintenance of structure and function of tissues depend on specific and regulated threedimensional organizations of the component cells and extracellular matrix constituents . Although the understanding of the mechanisms governing tissue organization remains as being one of the major unsolved mysteries in metazoan biology weknow thatprocesses such ashomotypic and heterotypic cell-cell adhesion, cellular interactions with extracellular matrix components, and cellular motility are central in tissue formation, tissue segregation, and maintenance of tissue boundaries. Cell-cell adhesion, that has a key role in this context, is mediated by cell adhesion molecules (CAMs), and it has been demonstrated that several CAMs are important for tissue formation during the embryonic development ofchickens and mice (8,24,32) . The mostwell-characterized CAMs in this respect are N-CAM and the cadherins (E-cadherin, N-cadherin, Rcadherin, and L-CAM) . N-CAM is a calcium-independent molecule belonging to the immunoglobulin superfamily (8) . The cadherins are calcium-dependent CAMs that mediate strong cell-cell binding in which interactions with actin-containing microfilaments are important (32) . It has recently been demonstrated that differential expression ofcadherins lead to sorting out ofmixed cell populations (9, 22), which is crucial for tissue segregation .Perturbation ofproper intercellular organization in the tissues causes malfunction . This is most dramatic in tumor invasion and metastasis, which not only involve abnormal or-0 The Rockefeller University Press, 0021-9525/91/