Document Detail


Endogenous interferon-gamma acts directly on tumor cells in vivo to suppress growth.
MedLine Citation:
PMID:  8806476     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Recent evidence implicates endogenous interferon-gamma (IFN-gamma) in the host response to an immunogenic tumor (MCA105); antibody blockade of host IFN-gamma increased tumor growth rate (Doherty et al., Ann. Surg. Oncol. 3: 198-203, 1996). Those experiments did not attempt to determine the site of IFN-gamma activity (the host, the tumor, or both). MATERIALS AND METHODS: MCA101 murine tumor cells were transfected with a plasmid expression vector containing an antisense construct to the IFN-gamma receptor (IFN-gamma R) or a control construct. Clones were isolated and tested for IFN-gamma stimulation of MHC I expression, sensitivity to IFN-gamma growth effects in vitro, and specific [125I]IFN-gamma binding. RESULTS: The antisense strategy was successful in decreasing the number of cell-surface IFN-gamma binding sites and in vitro response to IFN-gamma. Finally, in vivo experiments demonstrated significantly increased untransfected tumor growth rate in animals after blockade of endogenous IFN-gamma by a single dose of anti-IFN-gamma antibody and more rapid growth of the IFN-gamma R-deficient cells compared to controls. CONCLUSION: endogenous IFN-gamma has a direct effect on this less immunogenic tumor in vivo, which serves to slow growth and which is, at least partially, mediated through interferon-gamma receptors on the tumor cell.
Authors:
G M Doherty; K Tsung; B McCluskey; J A Norton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of surgical research     Volume:  64     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1996-12-05     Completed Date:  1996-12-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  68-74     Citation Subset:  IM    
Affiliation:
Department of Surgery, Washington University, St. Louis, Missouri 63110, USA. doherty@wudos2.wustl.edu
Data Bank Information
Bank Name/Acc. No.:
GENBANK/M28233
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / immunology
Antisense Elements (Genetics) / pharmacology
Base Sequence
Binding Sites
Cell Line, Transformed
Female
Histocompatibility Antigens Class I / immunology
Interferon-gamma / immunology,  metabolism,  physiology*
Mice
Mice, Inbred C57BL
Molecular Probes / genetics
Molecular Sequence Data
Neoplasms, Experimental / metabolism,  pathology*
Receptors, Cell Surface / genetics
Transfection
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antisense Elements (Genetics); 0/Histocompatibility Antigens Class I; 0/Molecular Probes; 0/Receptors, Cell Surface; 82115-62-6/Interferon-gamma

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