Differential autocrine regulation of intestine epithelial cell proliferation and differentiation by insulin-like growth factor (IGF) system components

The mechanisms which regulate cell turnover in the intestinal epithelium ar e incompletely understood. The present study was performed to characterize the role of autocrine IGF system components in intestine epithelial cell pr oliferation and differentiation comparing rapidly growing crypt cells (IEC- 6) with differentiating enterocytes (CaCo-2). The autocrine release of IGF- I, IGF-II and IGFBP-1 through -3 was determined by specific RIAs and wester n ligand blotting. In addition, binding and growth-promoting activity of in sulin, IGF-I and IGF-II was investigated. Enterocytic differentiation was a ssessed by measuring the brush-border enzymes alkaline phosphatase and sucr ase. During IEC-6 growth, the autocrine release of IGF-l and -II increased, whereas IGFBP-2 levels decreased. Specific receptors for IGF-I and IGF-II but not insulin could be detected. IGF-I was 100-fold more potent than insu lin to stimulate IEC-6 cell proliferation. In contrast, CaCo-2 cells reveal ed higher binding of insulin than ICF-I/-II and no release of ICF-I. At swi tch from CaCo2 cell proliferation to differentiation a marked increase in t he secretion of IGF-II (10-fold), IGFBP-1 (2.5-fold), IGFBP-2 (3-fold), and IGFBP-3 (6-fold) was measured. Our data indicate that IGF system component s differentially modulate enterocytic cell proliferation and differentiatio n.