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  • Author: Helmut J Kolb x
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Barbara Funk, Ulrike Kessler, Wolfgang Eisenmenger, Angela Hansmann, Helmut J Kolb and Wieland Kiess

The insulin-like growth factors (IGFs) are bound to multiple IGF binding proteins (IGFBPs) that are present both in the circulation and in extracellular fluids. There are at least six different IGFBP species that have been fully characterized in terms of molecular structure and amino acid sequence. The tissue distribution and local production of these proteins as well as the regulation of IGFBP production in different tissues have not been elucidated. We have studied the distribution of multiple IGFBP species in protein extracts from human kidney, skeletal muscle, lung, liver and brain by ligand blotting employing [125I]IGF-2 as the radiolabeled hormone. Five distinct IGFBP species with a respective molecular weight of43, 38, 34, 30 and 20 kDa were detected on the ligand blots in tissues from human fetuses and infants (23 weeks of gestation till 24 months of postnatal age). The 34 kDa species and a 30–32 kDa IGFBP species were predominant in brain, whereas a 30 kDa IGFBP species was mainly detected in skeletal muscle. Immunoblotting experiments using an anti IGFBP-2 antiserum showed that the 34 kDa IGFBP species from human brain was presumably related to IGFBP-2. We conclude that IGFBPs are differentially expressed in different tissues throughout human fetal life and early infancy. Local production or accumulation of the different IGFBPs could modulate IGF action at a local level or alternatively have differential functions during development.

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Andreas Hoeflich, Yi Yang, Wolfgang Rascher, Werner F Blum, Stefan Huber, Gabriele Koepf, Helmut J Kolb and Wieland Kiess

Hoeflich A, Yang Y, Rascher W, Blum WF, Huber S, Koepf G, Kolb HJ, Kiess W. Coordinate expression of insulin-like growth factor II (IGF-II) and IGF-II/mannose-6-phosphate receptor mRNA and stable expression of IGF-I receptor mRNA during differentiation of human colon carcinoma cells (Caco-2). Eur J Endocrinol 1996;135:49–59. ISSN 0804–4643

Insulin-like growth factor II (IGF-II) has been implicated in the differentiation of skeletal muscle cells. In this study the putative role of IGF-II in epithelial cell differentiation was investigated. The expression of IGF-II, IGF-1 receptor and IGF-II/mannose-6-phosphate receptor (IGF-II/M6P receptor) mRNA during spontaneous differentiation of the colon carcinoma cell line Caco-2 was measured. In addition, differentiation of Caco-2 cells during the cell culture period (days 1–21 in culture) was studied in parallel using morphological (light and scanning electron microscopy) and biochemical markers of growth (DNA, RNA and protein content, and β-actin mRNA and glyceraldehyde phosphate dehydrogenase mRNA expression) and differentiation (alkaline phosphatase activity, carcinoembryonic antigen content). A putative correlation between the markers of growth and differentiation and IGF gene expression was studied using linear regression analysis. Expression of IGF-II mRNA and IGF-II/M6P receptor mRNA correlated significantly with the progress of differentiation, while the IGF-I receptor was stably expressed throughout the culture period and exhibited a crucial role for the survival of Caco-2 cells, as shown by blocking experiments employing the monoclonal anti-IGF-I receptor antibody alpha-IR3. We hypothesize that: IGF-II mRNA and IGF-II/M6P receptor mRNA are expressed in a coordinate 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 IGF-II as a growth stimulant and for the IGF-II/M6P receptor for a regulator of IGF-II bioavailability in differentiating cells; alternatively, high IGF-II/M6P receptor mRNA and protein expression in differentiated cells but low IGF-II binding to the IGF-II/M6P receptor point to an important intracellular role of this receptor type in differentiated colon epithelial cells; the IGF-I receptor mRNA is stably expressed during the differentiation process of Caco-2 cells; the IGF-I receptor protein seems to be a prerequisite for the survival of Caco-2 cells.

W Kiess, Children's Hospital, Justus Liebig University, Feulgenstr. 12, D-35385 Giessen, Germany