| Cooperation between heparin-binding EGF-like growth factor and interleukin-6 in promoting the growth of human myeloma cells. | |
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MedLine Citation:
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PMID: 11971193 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Interleukin-6 (IL-6) is a major survival and proliferation factor of human malignant plasma cells and IL-6 dependent myeloma cell lines can be obtained from patients with terminal disease. We show here that mutated diphtheria toxin, a specific inhibitor of heparin-binding epidermal growth factor-like growth factor (HB-EGF), blocked the IL-6-induced growth of two myeloma cell lines (XG-1 and XG-14) and did not significantly affect that of two other cell lines (XG-6 and XG-13). The IL-6 mediated growth of myeloma cells was also inhibited by antibodies to ErbB1, a receptor for HB-EGF. The XG-1 and XG-14 cell lines that are sensitive to HB-EGF inhibitors overexpressed HB-EGF and EGF receptor (ErbB1) genes. They also overexpressed CD9, a tetraspanin that binds to the heparin-binding domain of HB-EGF and is critical for promoting ErbB1 activation by HB-EGF. The XG-6 and XG-13 myeloma cells that were not significantly sensitive to HB-EGF antagonists, poorly expressed HB-EGF, ErbB1 and CD9 genes or proteins. We demonstrated that recombinant HB-EGF supported the long-term growth of myeloma cells, as did IL-6. The myeloma cell growth factor activity of HB-EGF was completely inhited by antibodies to ErbB1, but also by antibodies to gp130 IL-6 transducer or to IL-6. These data indicate that in the XG-1 and XG-14 IL-6-dependent myeloma cell lines, the CD9/HB-EGF/erbB1 and the IL-6/IL-6R/gp130 pathways cooperate synergistically to trigger myeloma cell growth. They suggest that inhibitors of the EGF receptor or HB-EGF may be useful for inducing myeloma cell apoptosis in patients with multiple myeloma. |
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Authors:
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Yue Dan Wang; John De Vos; Michel Jourdan; Guilhem Couderc; Zhao-Yang Lu; Jean-François Rossi; Bernard Klein |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncogene Volume: 21 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2002 Apr |
Date Detail:
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Created Date: 2002-04-23 Completed Date: 2002-05-08 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 2584-92 Citation Subset: IM |
Affiliation:
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INSERM U475 and Unit for Cellular Therapy, CHU Montpellier, 99 Rue Puech Villa, 34197 Montpellier, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD
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metabolism Apoptosis Autocrine Communication Cell Division / drug effects Cell Survival / drug effects Dose-Response Relationship, Drug Drug Synergism Epidermal Growth Factor / pharmacology* Humans Intercellular Signaling Peptides and Proteins Interleukin-6 / pharmacology* Kinetics Membrane Glycoproteins* Models, Biological Multiple Myeloma / metabolism, pathology* RNA, Neoplasm / biosynthesis Receptor, Epidermal Growth Factor / genetics, metabolism Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/CD9 antigen; 0/Intercellular Signaling Peptides and Proteins; 0/Interleukin-6; 0/Membrane Glycoproteins; 0/RNA, Neoplasm; 149176-25-0/heparin-binding EGF-like growth factor; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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