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The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor

A plethora of myeloma growth factors (MGFs) has been identified, but their relative importance and cooperation have not been determined. We investigated 5 MGFs (interleukin-6 [IL-6], insulin-like growth factor type 1 [IGF-1], hepatocyte growth factor [HGF], HB-epidermal growth factor [HB-EGF], and a...

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Main Authors: Sprynski, Anne Catherine (Author) , Hose, Dirk (Author) , Caillot, Laurent (Author) , Réme, Thierry (Author) , Shaughnessy, John D., Jr (Author) , Barlogie, Bart (Author) , Seckinger, Anja (Author) , Moreaux, Jérôme (Author) , Hundemer, Michael (Author) , Jourdan, Michel (Author) , Meißner, Tobias (Author) , Jauch, Anna (Author) , Mahtouk, Karène (Author) , Kassambara, Alboukadel (Author) , Bertsch, Uta (Author) , Rossi, Jean François (Author) , Goldschmidt, Hartmut (Author) , Klein, Bernard (Author)
Format: Article (Journal)
Language:English
Published: [May 7 2009]
In: Blood
Year: 2009, Volume: 113, Issue: 19, Pages: 4614-4626
ISSN:1528-0020
DOI:10.1182/blood-2008-07-170464
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2008-07-170464
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Author Notes:Anne Catherine Sprynski, Dirk Hose, Laurent Caillot, Thierry Réme, John D., Jr Shaughnessy, Bart Barlogie, Anja Seckinger, Jérôme Moreaux, Michael Hundemer, Michel Jourdan, Tobias Meißner, Anna Jauch, Karène Mahtouk, Alboukadel Kassambara, Uta Bertsch, Jean François Rossi, Hartmut Goldschmidt, and Bernard Klein
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Summary:A plethora of myeloma growth factors (MGFs) has been identified, but their relative importance and cooperation have not been determined. We investigated 5 MGFs (interleukin-6 [IL-6], insulin-like growth factor type 1 [IGF-1], hepatocyte growth factor [HGF], HB-epidermal growth factor [HB-EGF], and a proliferation-inducing ligand [APRIL]) in serum-free cultures of human myeloma cell lines (HMCLs). In CD45− HMCLs, an autocrine IGF-1 loop promoted autonomous survival whereas CD45+ HMCLs could not survive without addition of MGFs, mainly IGF-1 and IL-6. IGF-1 was the major one: its activity was abrogated by an IGF-1R inhibitor only, whereas IL-6, HGF, or HB-EGF activity was inhibited by both IGF-1R- and receptor-specific inhibition. APRIL activity was inhibited by its specific inhibitor only. Of the investigated MGFs and their receptors, only expressions of IGF-1R and IL-6R in multiple myeloma cells (MMCs) of patients delineate a group with adverse prognosis. This is mainly explained by a strong association of IGF-1R and IL-6R expression and t(4;14) translocation, but IGF-1R expression without t(4;14) can also have a poor prognosis. Thus, IGF-1-targeted therapy, eventually in combination with anti-IL-6 therapy, could be promising in a subset of patients with MMCs expressing IGF-1R.
Item Description:Prepublished online as Blood first edition paper, February 24, 2009
Gesehen am 14.01.2022
Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2008-07-170464

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