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Insulin is a potent myeloma cell growth factor through insulin/IGF-1 hybrid receptor activation

Insulin and insulin growth factor type 1 (IGF-1) and their receptors are closely related molecules, but both factors bind to the receptor of the other one with a weak affinity. No study has presently documented a role of insulin as a myeloma growth factor (MGF) for human multiple myeloma cells (MMCs...

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Hauptverfasser: Sprynski, A. C. (VerfasserIn) , Hose, Dirk (VerfasserIn) , Kassambara, A. (VerfasserIn) , Vincent, L. (VerfasserIn) , Jourdan, M. (VerfasserIn) , Rossi, J. F. (VerfasserIn) , Goldschmidt, Hartmut (VerfasserIn) , Klein, B. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 16 September 2010
In: Leukemia
Year: 2010, Jahrgang: 24, Heft: 11, Pages: 1940-1950
ISSN:1476-5551
DOI:10.1038/leu.2010.192
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/leu.2010.192
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/leu2010192
Volltext
Verfasserangaben:A.C. Sprynski, D. Hose, A. Kassambara, L. Vincent, M. Jourdan, J.F. Rossi, H. Goldschmidt and B. Klein
Beschreibung
Zusammenfassung:Insulin and insulin growth factor type 1 (IGF-1) and their receptors are closely related molecules, but both factors bind to the receptor of the other one with a weak affinity. No study has presently documented a role of insulin as a myeloma growth factor (MGF) for human multiple myeloma cells (MMCs), whereas many studies have concluded that IGF-1 is a major MGF. IGF-1 receptor (IGF-1R) is aberrantly expressed by MMCs in association with a poor prognosis. In this study we show that insulin receptor (INSR) is increased throughout normal plasma cell differentiation. INSR gene is also expressed by MMCs of 203/206 newly diagnosed patients. Insulin is an MGF as potent as IGF-1 at physiological concentrations and requires the presence of insulin/IGF-1 hybrid receptors, stimulating INSR+IGF-1R+ MMCs, unlike INSR+IGF-1R− or INSR−IGF-1R− MMCs. Immunoprecipitation experiments indicate that INSR is linked with IGF-1R in MMCs and that insulin induces both IGF-1R and INSR phosphorylations and vice versa. In conclusion, we demonstrate for the first time that insulin is an MGF as potent as IGF-1 at physiological concentrations and its activity necessitates insulin/IGF-1 hybrid receptor activation. Further therapeutic strategies targeting the IGF/IGF-1R pathway have to take into account neutralizing the IGF-1R-mediated insulin MGF activity.
Beschreibung:Gesehen am 05.10.2023
Beschreibung:Online Resource
ISSN:1476-5551
DOI:10.1038/leu.2010.192

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