Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role.

A cDNA encoding the cell-cell adhesion molecule E-cadherin was transfected into highly invasive epithelial tumor cell lines of dog kidney or mouse mammary gland origin. Transfectants with a homogeneously high expression of E-cadherin showed a reproducible loss of activity in two types of in vitro invasion assays. Invasiveness of these transfectants could be reinduced specifically by treatment with anti-E-cadherin antibodies. In vivo, they formed partly differentiated tumors, instead of fully undifferentiated tumors. Alternatively, a plasmid encoding E-cadherin-specific anti-sense RNA was introduced into noninvasive ras-transformed cells with high endogenous E-cadherin expression. The resulting down-regulation, albeit partial, rendered the cells invasive. These data provide direct evidence that E-cadherin acts as an invasion suppressor molecule.