Document Detail


Loss of IL-6 receptor expression in cervical carcinoma cells inhibits autocrine IL-6 stimulation: abrogation of constitutive monocyte chemoattractant protein-1 production.
MedLine Citation:
PMID:  10925276     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IL-6 is synthesized in human papilloma virus (HPV)-transformed cervical carcinoma cell lines and is supposed to stimulate these cells in an autocrine manner. We studied IL-6 production and responsiveness in nonmalignant HPV-transformed keratinocytes and cervical carcinoma cells in detail. IL-6 was detected in cervical carcinomas in situ. Correspondingly, HPV-positive carcinoma cell lines expressed high IL-6 levels. However, these carcinoma cell lines showed low responsiveness to IL-6 as revealed by low constitutive STAT3 binding activity, which was not further enhanced by exogenous IL-6. In contrast, in vitro-transformed nonmalignant keratinocytes without endogenous IL-6 production strongly responded to exogenous IL-6 with activation of STAT3. STAT3 protein expression levels were comparable in both responsive and nonresponsive cell lines. Also, gp130, the upstream signal-transducing receptor subunit conveying IL-6 signals into the cell, was expressed in all tested cell lines. However, the IL-6 binding subunit gp80 was lost in the malignant cells. Addition of soluble gp80 was sufficient to restore IL-6 responsiveness in carcinoma cells as shown by enhanced activation of STAT3 binding activity. As a consequence of the restored IL-6 responsiveness, carcinoma cells strongly produced the chemokine monocyte chemoattractant protein-1 (MCP-1). Our data demonstrate that cervical carcinoma cells producing high amounts of IL-6 only weakly respond to IL-6 in an autocrine manner due to limited gp80 expression. While production of IL-6 might contribute to a local immunosuppressive effect, silencing an autocrine IL-6 response prevents constitutive production of the mononuclear cell-attracting chemokine MCP-1. Both mechanisms might help the tumor to escape the immune system.
Authors:
S Hess; H Smola; U Sandaradura De Silva; D Hadaschik; D Kube; S E Baldus; U Flucke; H Pfister
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  165     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-09-14     Completed Date:  2000-09-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1939-48     Citation Subset:  AIM; IM    
Affiliation:
Institute of Virology, University of Cologne, Cologne, Germany. s.hess@uni-koeln.de
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD95 / physiology
Apoptosis / immunology
Autocrine Communication / immunology*
Carcinoma in Situ / immunology,  metabolism,  pathology
Carcinoma, Squamous Cell / immunology,  metabolism,  pathology
Cell Line, Transformed
Chemokine CCL2 / antagonists & inhibitors*,  biosynthesis*
DNA-Binding Proteins / biosynthesis,  metabolism
Female
Humans
Interleukin-6 / antagonists & inhibitors*,  biosynthesis,  pharmacology,  physiology*
Receptors, Interleukin-6 / antagonists & inhibitors,  biosynthesis*,  physiology
STAT3 Transcription Factor
Signal Transduction / immunology
Solubility
Trans-Activators / biosynthesis,  metabolism
Tumor Cells, Cultured
Uterine Cervical Neoplasms / immunology*,  metabolism*,  pathology
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Chemokine CCL2; 0/DNA-Binding Proteins; 0/Interleukin-6; 0/Receptors, Interleukin-6; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Trans-Activators; 0/interleukin-6 receptor alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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