Profile of IGF-binding proteins secreted by intestinal epithelial cells changes with differentiation.
Previous reports have shown that gastrointestinal epithelial cells produce insulin-like growth factor-binding proteins (IGF-BP), which modulate the actions of IGF. This study aims to examine the relationship between differentiation and IGF-BP secretion by human intestinal epithelial cells and the effect of growth factors on their production. Caco-2 cells were cultured in serum-free media. IGF-BP secretion into the incubation media was analyzed by Western 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 stages of differentiation. IGF-I stimulated mainly IGF-BP-3 production, but epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulated predominantly IGF-BP-4 secretion. Adding an anti-EGF receptor antibody to block autocrine TGF-alpha activity inhibited IGF-BP-4 production but stimulated IGF-BP-2 and IGF-BP-3. In conclusion, the profile of IGF-BP secretion changes with differentiation. IGF-I and EGF (or TGF-alpha) stimulate different types of IGF-BP, with autocrine TGF-alpha activity being a factor affecting IGF-BP production during differentiation.
Oguchi
S
S
Developmental Gastroenterology Laboratory, Massachusetts General Hospital, Boston 02129.
Walker
W A
WA
Sanderson
I R
IR
D000906:Antibodies / Q000494:pharmacology; D002352:Carrier Proteins / Q000145:classification / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D066246:ErbB Receptors / Q000276:immunology; D006728:Hormones / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism
D000906:Antibodies; D002352:Carrier Proteins; D006728:Hormones; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors