The mechanisms which regulate cell turnover in the intestinal epithelium are incompletely
understood. The present study was performed to characterize the role of autocrine
IGF system components in intestine epithelial cell proliferation 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 western ligand blotting. In addition, binding and growth-promoting activity
of insulin, IGF-I and IGF-II was investigated. Enterocytic differentiation was assessed
by measuring the brush-border enzymes alkaline phosphatase and sucrase. During IEC-6
growth, the autocrine release of IGF-I 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 insulin to stimulate IEC-6 cell proliferation. In contrast,
CaCo-2 cells revealed higher binding of insulin than IGF-I/-II and no release of IGF-I.
At switch from CaCo2 cell proliferation to differentiation a marked increase in the
secretion of IGF-II (10-fold), IGFBP-I (2.5-fold), IGFBP-2 (3-fold), and IGFBP-3 (6-fold)
was measured. Our data indicate that IGF system components differentially modulate
enterocytic cell proliferation and differentiation.
Key words
Intestine Epithelial Cells - Insulin-Like Growth Factors - Insulin-Like Growth Factor
Binding Proteins
