Differentiation and polarity alter the binding of IGF-I to human intestinal epithelial (Caco-2) cells.

This study examined whether insulin-like growth factor-I (IGF-I) bound to specific functioning IGF receptors on the surface of Caco-2 cells and how this binding was affected by the differentiation and polarity of these cells. IGF-I, which increased cell proliferation in a dose-dependent manner, bound to a specific receptor on the surface of Caco-2 cells. Affinity cross-linking with labeled IGF-I followed by reducing sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed M(r)s at 135,000, 270,000 and 355,000 bands, which was inhibited by unlabeled IGF-I. A Scatchard analysis of radioligand-receptor binding showed the presence of a single class of receptors with high affinity for IGF-I. This class of receptors was specific for IGF-I, the affinity of IGF-I to the receptor being four and 150 times greater than IGF-II and insulin, respectively. There was no difference in the affinity of IGF-I to type 1 IGF receptors between less-differentiated [dissociation constant (Kd) = 3.81 nM] and well-differentiated cells (Kd = 3.78 nM); however, well-differentiated cells showed a 2.4-fold higher maximum number of binding sites (Bmax) than less-differentiated cells (3.45 vs. 1.44 x 10(4) sites/cell), indicating an increase in the density of IGF-I receptors with differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)