E-cadherin is considered to be an invasion suppressor molecule. We have studied the expression and function of E-cadherin in three cell lines derived from a dog mammary tumor, namely SH15, SH24, and SH27. In monolayer culture the cell lines can be distinguished by their morphotype: epithelioid (SH15), fibroblast-like (SH24) and intermediate type (SH27). SH27 was unable to form colonies in collagen gel in contrast to SH15 and SH24. All three cell lines expressed the E-cadherin antigen, as evident from immunocytochemistry, and alpha-, beta-, and gamma-catenins as evident from immunoprecipitation with E-cadherin antibody. Only SH27 showed E-cadherin-dependent aggregation, and little invasion into collagen type 1 gels, in contrast to SH15 and SH24 cells. However, in the precultured embryonic chick heart assay all three cell lines were invasive, demonstrating that invasion depends upon the microenvironment. We assume that in the embryonic chick heart, factors were present or were induced by the SH27 cells, interfering with the function of E-cadherin.