Regulation of the insulin-like growth factor axis by increasing cell number in intestinal epithelial (IEC-6) cells

Insulin-like growth factor binding protein-2 (IGFBP-2) production as a function of cell number by intestinal epithelial cells (IEC-6) was regulated such that the IGFBP-2 concentration in 24-h conditioned medium reached a maximum, which was maintained despite increasing cell number. Northern blot analysis revealed that this effect could largely be attributed to decreasing IGFBP-2 mRNA. In contrast to IGFBP-2, secretion of IGF-II and accumulation of IGF-II mRNA by IEC-6 cells correlated positively with cell number. The highest level of IGF-II protein detected by immunoblotting of conditioned medium occurred in post-confluent cells. IGF-I stimulated the cells to grow to a high cellular density and inhibited IGFBP-2 secretion in a concentration-dependent fashion. We conclude that expression of IGF-II and IGFBP-2 are regulated in IEC-6 cells by cellular density, and IGF-II may act as a survival factor at high cell density.