Summary
Binding studies using recombinant human125I-labelled insulin-like growth factor I ([125I]IGF-I) revealed IGF-I receptors in three Ewing's sarcoma cell lines withK d ranging from 74×10−12 M to 100×10−12 M andB max=36–63 fmol/mg cell protein. [125I]IGF-I binding was displaced by IGF-I, IGF-II and insulin with IC50 values of 1.5 nM, 6.3 nM and 0.7 μM respectively. Recombinant human [125I]IGF-II radioligand-binding assays in the cell lines disclosed specific binding sites for IGF-II withK d=(110–175)×10−12 M andB max varying from 21 fmol/mg to 72 fmol/mg cell protein. Neither IGF-I nor insulin displaced [125I]IGF-II binding. IGF-I was found to increase basal glucose transport by maximally 1.5 times with EC50=0.9 nM IGF-I. The efficacy and potency of IGF-II on glucose uptake were comparable to those of IGF-I whereas insulin was ineffective. IGF-I and IGF-II also provoked stimulation of glycogen synthesis in Ewing's sarcoma cells. The maximal glycogenic response was reached at 0.01 μM IGF-I and 0.1 μM IGF-II, the EC50 value being approximately 1 nM IGF-I and 2 nM IGF-II. Insulin did not significantly influence glycogen formation. IGF-I and IGF-II but not insulin increased DNA synthesis in Ewing's sarcoma cells. The maximal mitogenic response was obtained with 10 nM IGF-I or IGF-II with an EC50 value of about 0.7 nM for both peptides. α-IR-3, a monoclonal antibody specific for the IGF type I receptor, effectively blocked IGF-I- and IGF-II-mediated metabolic responses. In conclusion, the data show that IGF-I and IGF-II induce rapid and longterm biological responses in Ewing's sarcoma cells exclusively through interaction with IGF type I receptors.
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van Valen, F., Winkelmann, W. & Jürgens, H. Type I and type II insulin-like growth factor receptors and their function in human Ewing's sarcoma cells. J Cancer Res Clin Oncol 118, 269–275 (1992). https://doi.org/10.1007/BF01208615
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DOI: https://doi.org/10.1007/BF01208615