EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR (IGF)-II AND IGF-I RECEPTOR DURING PROLIFERATION AND DIFFERENTIATION OF CACO-2 HUMAN COLON-CARCINOMA CELLS

We have studied the expression of insulin-like growth factor type II ( ICF-II) and its autocrine role during the proliferation and differenti ation of the CaCo-2 colon carcinoma cell line. IGF-II RNA levels were high in proliferating cells and decreased by more than 10-fold when ce lls ceased to proliferate and differentiated. Immunoreactive IGF-II pr otein was high in the conditioned media of proliferating cells and dec reased 20-fold in the media of differentiated cells. Reduced IGF-II ex pression was associated with a decrease in ICF-I receptor number that was high in proliferating cells (approximately 80,000 binding sites/ce ll) and reduced by 4-fold in differentiated cells. Exogenously added I GF-II was able to stimulate proliferation of serum-deprived cells in a dose-dependent fashion. IGF-II acted through the IGF-I receptor, sinc e both basal and IGF-II-stimulated cell proliferation was inhibited by the monoclonal antibody alpha-IR3, which blocks the binding sites of the ICF-I receptor. The inhibition of CaCo-2 basal cell growth by the alpha-IR3 antibody suggests that ICF-II may act as an autocrine growth factor for these cells.