The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor
Open Access
- 7 May 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 113 (19), 4614-4626
- https://doi.org/10.1182/blood-2008-07-170464
Abstract
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.Keywords
This publication has 52 references indexed in Scilit:
- A new method for class prediction based on signed-rank algorithms applied to Affymetrix® microarray experimentsBMC Bioinformatics, 2008
- Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic ApplicationsClinical Cancer Research, 2007
- Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancerNature Reviews Drug Discovery, 2007
- Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myelomaBlood, 2007
- Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du MyélomeBlood, 2007
- A Meta-Analysis of Human Embryonic Stem Cells Transcriptome Integrated into a Web-Based Expression AtlasThe International Journal of Cell Cloning, 2007
- The molecular classification of multiple myelomaBlood, 2006
- Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myelomaOncogene, 2006
- A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains anIGH/MMSET fusion transcriptBlood, 2003
- Major role of the soluble interleukin‐6/interleukin‐6 receptor complex for the proliferation of interleukin‐6‐dependent human myeloma cell linesEuropean Journal of Immunology, 1997