Document Detail


Multiple myeloma cells catalyze hepatocyte growth factor (HGF) activation by secreting the serine protease HGF-activator.
MedLine Citation:
PMID:  15172968     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Esther P M Tjin; Patrick W B Derksen; Hiroaki Kataoka; Marcel Spaargaren; Steven T Pals
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Publication Detail:
Type:  Journal Article     Date:  2004-06-01
Journal Detail:
Title:  Blood     Volume:  104     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-20     Completed Date:  2004-11-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2172-5     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
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:
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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