INSULIN-LIKE GROWTH FACTOR-I ACTIVATES THE INVASION SUPPRESSOR FUNCTION OF E-CADHERIN IN MCF-7 HUMAN MAMMARY-CARCINOMA CELLS IN-VITRO

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mm CaCl2, and they were invasive after confrontation.with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 mug ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alphaIR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation.-The effects of IGF-I on aggregation and on invasion could be mimicked by 1 mug ml-1 insulin, but not by 0.5 mug ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alphaIR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells.