| Multiple myeloma cells catalyze hepatocyte growth factor (HGF) activation by secreting the serine protease HGF-activator. | |
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MedLine Citation:
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PMID: 15172968 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Multiple myeloma (MM) is a common hematologic neoplasm consisting of malignant plasma cells, which expand in the bone marrow. A potential key signal in the evolution of MM is hepatocyte growth factor (HGF), which acts as a potent paracrine and/or autocrine growth factor and survival factor for MM cells. Proteolytic conversion of HGF into its active form is a critical limiting step in HGF/MET signaling. Here, we show that malignant MM plasma cells convert HGF into its active form and secrete HGF-activator (HGFA), a serine protease specific for HGF activation. By using serine protease inhibitors and neutralizing antibodies, we demonstrate that HGFA produced by the MM cells is responsible for their ability to catalyze HGF activation. We, therefore, suggest that autocatalyzation of HGF conversion by MM cells is an important step in HGF/MET-induced myeloma growth and survival, which may have implications for the management of this incurable form of cancer. |
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Authors:
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Esther P M Tjin; Patrick W B Derksen; Hiroaki Kataoka; Marcel Spaargaren; Steven T Pals |
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Publication Detail:
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Type: Journal Article Date: 2004-06-01 |
Journal Detail:
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Title: Blood Volume: 104 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2004 Oct |
Date Detail:
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Created Date: 2004-09-20 Completed Date: 2004-11-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 2172-5 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Animals Blotting, Western COS Cells Catalysis Cell Line, Tumor Cell Separation Culture Media, Conditioned / pharmacology Enzyme Activation Flow Cytometry Hepatocyte Growth Factor / metabolism* Humans Immunohistochemistry Liver / metabolism Male Models, Biological Multiple Myeloma / metabolism*, pathology Precipitin Tests Serine Endopeptidases / secretion* Time Factors Transfection |
| Chemical | |
Reg. No./Substance:
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0/Culture Media, Conditioned; 67256-21-7/Hepatocyte Growth Factor; EC 3.4.21.-/HGF activator; EC 3.4.21.-/Serine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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