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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:113 |
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| Enthalten in: |
Blood - 113(2009), 19 vom: 07. Mai, Seite 4614-26 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sprynski, Anne Catherine [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.06.2009 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1182/blood-2008-07-170464 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM186541120 |
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| 041 | |a eng | ||
| 100 | 1 | |a Sprynski, Anne Catherine |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor |
| 264 | 1 | |c 2009 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 09.06.2009 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Culture Media, Serum-Free |2 NLM | |
| 650 | 7 | |a HBEGF protein, human |2 NLM | |
| 650 | 7 | |a HGF protein, human |2 NLM | |
| 650 | 7 | |a Heparin-binding EGF-like Growth Factor |2 NLM | |
| 650 | 7 | |a Intercellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Receptors, Interleukin-6 |2 NLM | |
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| 650 | 7 | |a Tumor Necrosis Factor Ligand Superfamily Member 13 |2 NLM | |
| 650 | 7 | |a Hepatocyte Growth Factor |2 NLM | |
| 650 | 7 | |a 67256-21-7 |2 NLM | |
| 650 | 7 | |a Insulin-Like Growth Factor I |2 NLM | |
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| 650 | 7 | |a Receptor, IGF Type 1 |2 NLM | |
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| 650 | 7 | |a Leukocyte Common Antigens |2 NLM | |
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| 700 | 1 | |a Hose, Dirk |e verfasserin |4 aut | |
| 700 | 1 | |a Caillot, Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Réme, Thierry |e verfasserin |4 aut | |
| 700 | 1 | |a Shaughnessy, John D |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Barlogie, Bart |e verfasserin |4 aut | |
| 700 | 1 | |a Seckinger, Anja |e verfasserin |4 aut | |
| 700 | 1 | |a Moreaux, Jérôme |e verfasserin |4 aut | |
| 700 | 1 | |a Hundemer, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Jourdan, Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Meissner, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Jauch, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Mahtouk, Karène |e verfasserin |4 aut | |
| 700 | 1 | |a Kassambara, Alboukadel |e verfasserin |4 aut | |
| 700 | 1 | |a Bertsch, Uta |e verfasserin |4 aut | |
| 700 | 1 | |a Rossi, Jean François |e verfasserin |4 aut | |
| 700 | 1 | |a Goldschmidt, Hartmut |e verfasserin |4 aut | |
| 700 | 1 | |a Klein, Bernard |e verfasserin |4 aut | |
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