N-CADHERIN PROMOTES ADHESION BETWEEN INVASIVE BREAST-CANCER CELLS ANDTHE STROMA

Calcium-dependent eel adhesion molecules (cadherins) are involved in m aintaining the epithelial structure of a number of tissues including t he mammary gland. In breast and other tumor types, loss of E-cadherin expression has been seen in high grade turners and correlates with inc reased invasiveness. Here we show high levels of expression of N-cadhe rin in the most invasive breast cancer cell lines which was inversely correlated with their expression of E-cadherin. A stromal cell line al so expressed N-cadherin in accordance with its fibroblastic morphology . N-cadherin localized to areas of cell-cell contact in all cells that expressed it. Calcium-dependent intercellular adhesion of N-cadherin- expressing breast cancer and stromal cells was specifically inhibited by an anti N-cadherin monoclonal antibody. In addition, N-cadherin pro moted the interaction of invasive breast cancer cells with mammary str omal cells; in contrast, E-cadherin expressing cell lines did not co-a ggregate with stromal cells. The combined results suggest a functional role for N-cadherin in cohesion of breast tumor cells which, in addit ion promotes their interaction with the surrounding stromal cells, the reby facilitating invasion and metastasis.