EXPRESSION OF IGF-II AND IGF BINDING-PROTEINS IN DIFFERENTIATING HUMAN INTESTINAL CACO-2 CELLS

Expression of IGF-II and IGF binding proteins in differentiating human intestinal Caco-2 cells. Am. J. Physiol. 269 (Endocrinol. Metab. 32): E804-E813, 1995.-The mitogenic and metabolic effects of insulin-like growth factor-II (IGF-II) can be modulated by six distinct IGF binding proteins (IGFBPs). As a first step toward understanding the role of I GFs and their binding proteins in intestinal epithelial cell different iation, the expression of IGF-II and IGFBPs was characterized in the h uman colon adenocarcinoma Caco-2 cell line. Northern blot analysis rev ealed two IGF-II transcripts of 5.4 and 4.5 kb, and ribonuclease prote ction assays indicated that IGF-II mRNA levels are regulated during Ca co-2 differentiation. A specific radioimmunoassay detected IGF-II in s erum-free conditioned medium, the level of which was three- to fivefol d higher in proliferating cells than in differentiated cells. Immunopr ecipitation and ligand blot-analyses of conditioned medium demonstrate d that IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-6 are synthesized by Caco- 2 cells, with IGFBP-8 and IGFBP-4 being the major IGFBPs secreted, and that the levels of IGFBP-2 and IGFBP-6 decreased as differentiation p roceeded. These results indicate that the expression of IGF-II, IGFBP- 8, and IGFBP-6 is regulated in a differentiation-dependent manner in C aco-2 cells.