COORDINATE EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-II (IGF-II) AND IGF-II MANNOSE-6-PHOSPHATE RECEPTOR MESSENGER-RNA AND STABLE EXPRESSIONOF IGF-I RECEPTOR MESSENGER-RNA DURING DIFFERENTIATION OF HUMAN COLON-CARCINOMA CELLS (CACO-2)/

Insulin-like growth factor II (IGF-II) has been implicated in the diff erentiation of skeletal muscle cells. In this study the putative role of IGF-II in epithelial cell differentiation was investigated. The exp ression of IGF-IT, IGF-I receptor and IGP-II/mannose-6-phosphate recep tor (IGF-II/M6P receptor) mRNA during spontaneous differentiation of t he colon carcinoma cell line Caco-2 was measured. In addition, differe ntiation of Caco-2 cells during the cell culture period (days 1-21 in culture) was studied in parallel using morphological (light and scanni ng electron microscopy) and biochemical markers of growth (DNA, RNA an d protein content, and beta-actin mRNA and glyceraldehyde phosphate de hydrogenase mRNA expression) and differentiation (alkaline phosphatase activity, carcinoembryonic antigen content). A putative correlation b etween the markers of growth and differentiation and IGF gene expressi on was studied using linear regression analysis. Expression of IGF-II mRNA and IGF-II/M6P receptor mRNA correlated significantly with the pr ogress of differentiation, while the IGF-I receptor was stably express ed throughout the culture period and exhibited a crucial role for the survival of Caco-2 cells, as shown by blocking experiments employing t he monoclonal anti-IGF-I receptor antibody alpha-IRS. We hypothesize t hat: IGF-II mRNA and IGF-II-/M6P receptor mRNA are expressed in a coor dinate fashion during the differentiation of Caco-2 cells; coordinate expression of IGF-II and of IGF-II/M6P receptor mRNA might point to a role for ICE-Il as a growth stimulant and for the IGF-II/M6P receptor for a regulator of ICE-II bioavailability in differentiating cells; al ternatively, high IGF-II/M6P receptor mRNA and protein expression in d ifferentiated cells but low IGF-IT binding to the IGF-II/M6P receptor point to an important intracellular role of this receptor type in diff erentiated colon epithelial cells; the IGF-I receptor mRNA is stably e xpressed during the differentiation process of Caco-2 cells; the ICE-I receptor protein seems to be a prerequisite for the survival of Caco- 2 cells.