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Expression of EGF-family receptors and amphiregulin in multiple myeloma. Amphiregulin is a growth factor for myeloma cells

A hallmark of plasma cells is the expression of syndecan-1, which has major functions in epithelial cells, in particular as the coreceptor of heparin-binding growth factors. We previously found that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a growth factor for malignant...

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Main Authors: Mahtouk, Karène (Author) , Hose, Dirk (Author) , Rème, Thierry (Author) , De Vos, John (Author) , Jourdan, Michel (Author) , Moreaux, Jérôme (Author) , Fiol, Geneviève (Author) , Raab, Marc-Steffen (Author) , Jourdan, Eric (Author) , Grau, Véronique (Author) , Moos, Marion (Author) , Goldschmidt, Hartmut (Author) , Baudard, Marion (Author) , Rossi, Jean François (Author) , Cremer, Friedrich Walter (Author) , Klein, Bernard (Author)
Format: Article (Journal)
Language:English
Published: 28 February 2005
In: Oncogene
Year: 2005, Volume: 24, Issue: 21, Pages: 3512-3524
ISSN:1476-5594
DOI:10.1038/sj.onc.1208536
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.onc.1208536
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/1208536
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Author Notes:Karène Mahtouk, Dirk Hose, Thierry Rème, John De Vos, Michel Jourdan, Jérôme Moreaux, Geneviève Fiol, Marc Raab, Eric Jourdan, Véronique Grau, Marion Moos, Hartmut Goldschmidt, Marion Baudard, Jean François Rossi, Friedrich W. Cremer, Bernard Klein
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Summary:A hallmark of plasma cells is the expression of syndecan-1, which has major functions in epithelial cells, in particular as the coreceptor of heparin-binding growth factors. We previously found that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a growth factor for malignant plasma cells. As amphiregulin (AREG) is another heparin-binding factor of the EGF family, we investigated its role in multiple myeloma (MM). Using Affymetrix DNA microarrays, we show here that the AREG gene was expressed by purified primary myeloma cells from 65 patients and that the expression was higher than in normal bone marrow (BM) plasma cells or plasmablastic cells. AREG stimulated IL-6 production and growth of BM stromal cells. Using real-time reverse transcriptase-polymerase chain reaction, we found that MM cells expressed ErbB receptors and that AREG promoted their growth. Furthermore, PD169540 (a pan-ErbB inhibitor) and IRESSA (an ErbB1-specific inhibitor) induced apoptosis of primary myeloma cells from 10/14 and 4/14 patients, respectively, and there was a synergistic effect with dexamethasone. Altogether, our data provide strong evidence that AREG plays an important role in the biology of MM and emphasize the advantages of using ErbB inhibitors, which might target myeloma cells as well as the tumor environment.
Item Description:Gesehen am 25.02.2022
Physical Description:Online Resource
ISSN:1476-5594
DOI:10.1038/sj.onc.1208536

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