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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1829-1837. Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-05-1510. This Article Full Text (PDF) All Versions of this Article: 2003-05-1510v1 103/5/1829    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mahtouk, K. Articles by Klein, B. Search for Related Content PubMed PubMed Citation Articles by Mahtouk, K. Articles by Klein, B. Social Bookmarking                   What's this? Submitted May 13, 2003 Accepted October 16, 2003 An inhibitor of the EGF receptor family blocks myeloma cell growth factor activity of HB-EGF and potentiates dexamethasone or anti-IL-6 antibody-induced apoptosis Karene Mahtouk, Michel Jourdan, John De Vos, Catherine Hertogh, Genevieve Fiol, Eric Jourdan, Jean-Francois Rossi, and Bernard Klein* INSERM U475 and Unit for Cellular Therapy, CHU Montpellier, Montpellier, France * Corresponding author; email: klein{at}montp.inserm.fr. We previously found that some myeloma cell lines express the heparin-binding epidermal growth factor-like growth factor (HB-EGF) gene. As the proteoglycan syndecan-1 is an HB-EGF coreceptor as well as a hallmark of plasma cell differentiation and a marker of myeloma cells, we studied the role of HB-EGF on myeloma cell growth. The HB-EGF gene was expressed by bone marrow mononuclear cells of 8/8 patients with myeloma, particularly by monocytes and stromal cells, but not by purified primary myeloma cells. 6/9 myeloma cell lines and 9/9 purified primary myeloma cells expressed ErbB1 or ErbB4 genes coding for HB-EGF receptor. In the presence of a low IL-6 concentration, HB-EGF stimulated the proliferation of the six ErbB1+ or ErbB4+ cell lines, through the PI-3K/AKT pathway. A pan-ErbB inhibitor blocked the myeloma cell growth factor activity and the signaling induced by HB-EGF. This inhibitor induced apoptosis of patients' myeloma cells cultured with their tumor environment. It also increased patients' myeloma cell apoptosis induced by an anti-IL-6 antibody or dexamethasone. The ErbB inhibitor had no effect on the interaction between MM cells and stromal cells. It was not toxic for non-myeloma cells present in patients' bone marrow cultures or for the growth of hematopoietic progenitors. Altogether, these data identify ErbB receptors as putative therapeutic targets in multiple myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. C. Sprynski, D. Hose, L. Caillot, T. Reme, J. D. Shaughnessy Jr, B. Barlogie, A. Seckinger, J. Moreaux, M. Hundemer, M. Jourdan, et al. The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor Blood, May 7, 2009; 113(19): 4614 - 4626. [Abstract] [Full Text] [PDF] X. Li, A. Pennisi, and S. Yaccoby Role of decorin in the antimyeloma effects of osteoblasts Blood, July 1, 2008; 112(1): 159 - 168. [Abstract] [Full Text] [PDF] K. Mahtouk, D. Hose, J. De Vos, J. Moreaux, M. Jourdan, J. F. Rossi, T. Reme, H. Goldschmidt, and B. Klein Input of DNA Microarrays to Identify Novel Mechanisms in Multiple Myeloma Biology and Therapeutic Applications Clin. 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