Document Detail


Functional significance of novel neurotrophin-1/B cell-stimulating factor-3 (cardiotrophin-like cytokine) for human myeloma cell growth and survival.
MedLine Citation:
PMID:  14632778     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytokines of the gp130 family, particularly interleukin 6 (IL-6), play a central role in the growth and survival of malignant plasma cells. Recently, novel neurotrophin-1 (NNT-1)/B cell-stimulating factor-3 (BSF-3), also reported as cardiotrophin-like cytokine (CLC), was identified as a cytokine belonging to the gp130 family. BSF-3, similar to IL-6, exerts regulatory effects on normal B cell functions, but its functional significance in haematological malignancies has not been defined. The purpose of this study was to evaluate the biological effects and signalling pathways that are induced by BSF-3 in malignant plasma cells. Recombinant human BSF-3 was found to have growth stimulatory activity on plasmacytoma cell lines and primary tumour cells. In addition, BSF-3 was able to protect from Dexamethasone (Dex)-induced apoptosis. BSF-3 stimulated cell growth could not be inhibited by neutralizing anti-IL-6 or anti-IL-6 receptor antibodies, but was abrogated by anti-gp130 antibodies. In INA-6.Tu11 cells, a subline of the IL-6-dependent human plasma cell line INA-6 expressing gp130 and the receptor for leukaemia inhibitory factor (LIF), stimulation with BSF-3 induced tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). AG490, an inhibitor of Janus kinases, decreased BSF-3 induced cell growth in a dose-dependent manner. This correlated with a reduction of STAT3 phosphorylation levels, while p44/42 mitogen-activated protein kinase (MAPK) phosphorylation was not affected. In conclusion, BSF-3 is a novel myeloma growth and survival factor with a potential role in the pathophysiology of the disease.
Authors:
Renate Burger; Frank Bakker; Andreas Guenther; Wolfgang Baum; Dirk Schmidt-Arras; Teru Hideshima; Yu-Tzu Tai; Reshma Shringarpure; Laurence Catley; Giorgio Senaldi; Martin Gramatzki; Kenneth C Anderson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of haematology     Volume:  123     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-11-24     Completed Date:  2004-01-23     Revised Date:  2008-09-10    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  869-78     Citation Subset:  IM    
Affiliation:
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / pharmacology
Antigens, CD / immunology
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Cell Division
Cytokine Receptor gp130
Cytokines / metabolism,  pharmacology
DNA-Binding Proteins / metabolism
Dexamethasone / pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Humans
Membrane Glycoproteins / immunology
Multiple Myeloma / metabolism*,  pathology
Phosphorylation
Recombinant Proteins / pharmacology
STAT3 Transcription Factor
Signal Transduction*
Trans-Activators / metabolism
Tumor Cells, Cultured
Tyrphostins / pharmacology
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD; 0/Antineoplastic Agents; 0/Cytokines; 0/DNA-Binding Proteins; 0/Enzyme Inhibitors; 0/IL6ST protein, human; 0/Membrane Glycoproteins; 0/Recombinant Proteins; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Trans-Activators; 0/Tyrphostins; 0/alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; 0/cardiotrophin-like cytokine; 133483-10-0/Cytokine Receptor gp130; 50-02-2/Dexamethasone

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