Type I and type II insulin-like growth factor receptors and their function in human Ewing's sarcoma cells |
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Authors: | F van Valen W Winkelmann H Jürgens |
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Institution: | (1) Kinderklinik, Abt. für Pädiatrische Hämatologie und Onkologie, Heinrich-Heine-Universität, Moorenstrasse 5, D-400 Düsseldorf, Federal Republic of Germany;(2) Orthopädische Klinik, Heinrich-Heine-Universität, Moorenstrasse 5, D-4000 Düsseldorf, Federal Republic of Germany;(3) Klinik und Poliklinik für Kinderheilkunde, Pädiatrische Hämatologie und Onkologie, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Strasse 33, W-4400 Münster, Federal Republic of Germany |
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Abstract: | 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 M 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 M IGF-I and 0.1 M 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. -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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Keywords: | Insulin-like growth factor receptor Glucose transport Glycogen synthesis DNA synthesis Ewing's sarcoma cells |
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