The expression of E-cadherin has been implicated in tumor metastasis, often as a tumor suppressor, but also as a promoter of growth and metastasis. We have shown that the functional activity of E-cadherin at the cell surface is often modified in response to environmental factors, and have developed monoclonal antibodies (mAbs) that activate E-cadherin adhesive function. These activating mAbs inhibit the metastasis of endogenous genetically driven mammary tumors in mice, and we dissect the process to show that these mAbs work at multiple steps of the metastatic cascade, including local invasion, intravasation, cell survival, and extravasation into the target organ. Thus, the functional state of E-cadherin is an important determinant of metastatic potential beyond whether the gene is expressed.
