Me. Bracke et al., INSULIN-LIKE GROWTH FACTOR-I ACTIVATES THE INVASION SUPPRESSOR FUNCTION OF E-CADHERIN IN MCF-7 HUMAN MAMMARY-CARCINOMA CELLS IN-VITRO, British Journal of Cancer, 68(2), 1993, pp. 282-289
The calcium-dependent cell-cell adhesion molecule E-cadherin has been
shown to counteract invasion of epithelial neoplastic cells. Using thr
ee monoclonal antibodies, we have demonstrated the presence of E-cadhe
rin at the surface of human MCF-7/6 mammary carcinoma cells by indirec
t immunofluorescence coupled to flow cytometry and by immunocytochemis
try. Nevertheless, MCF-7/6 cells failed to aggregate in a medium conta
ining 1.25 mm CaCl2, and they were invasive after confrontation.with e
mbryonic 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 ho
motypic aggregation within 5 to 10 min and inhibited invasion in vitro
during at least 8 days. The effect of IGF-I on cellular aggregation w
as insensitive to cycloheximide. However, monoclonal antibodies that i
nterfered 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 eff
ects were presumably not mediated by the IGF-I receptor, since they co
uld not be blocked by an antibody against this receptor (alphaIR3). Ou
r results indicate that IGF-I activates the invasion suppressor role o
f E-cadherin in MCF-7/6 cells.