PROFILE OF IGF-BINDING PROTEINS SECRETED BY INTESTINAL EPITHELIAL-CELLS CHANGES WITH DIFFERENTIATION

Profile of IGF-binding proteins secreted by intestinal epithelial cell s changes with differentiation. Am. J. Physiol. 267 (Gastrointest. Liv er Physiol. 30): G843-G850, 1994.-Previous reports have shown that gas trointestinal epithelial cells produce insulin-like growth factor-bind ing proteins (IGF-BP), which modulate the actions of IGF. This study a ims to examine the relationship between differentiation and IGF-BP sec retion by human intestinal epithelial cells and the effect of growth f actors on their production. Caco-2 cells were cultured in serum-free m edia. IGF-BP secretion into the incubation media was analyzed by Weste rn ligand blotting and immunoblotting. Caco-2 cells produced IGF-BP-2, IGF-BP-3, and IGF-BP-4. Secretion of IGF-BP-2 and IGF-BP-3 increased with differentiation, but IGF-BP-4 secretion diminished. The effect of exogenous growth factors on IGF-BP secretion was maximal at earlier s tages of differentiation. IGF-I stimulated mainly IGF-BP-3 production, but epidermal growth factor (EGF) and transforming growth factor-alph a (TGF-alpha) stimulated predominantly IGF-BP-4 secretion. Adding an a nti-EGF receptor antibody to block autocrine TGF-alpha activity inhibi ted IGF-BP-4 production but stimulated IGF-BP-S and IGF-BP-3. In concl usion, the profile of IGF-BP secretion changes with differentiation. I GF-I and EGF (or TGF-alpha) stimulate different types of IGF-BP, with autocrine TGF-alpha activity being a factor affecting IGF-BP productio n during differentiation.