| Loss of IL-6 receptor expression in cervical carcinoma cells inhibits autocrine IL-6 stimulation: abrogation of constitutive monocyte chemoattractant protein-1 production. | |
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MedLine Citation:
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PMID: 10925276 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 165 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2000 Aug |
Date Detail:
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Created Date: 2000-09-14 Completed Date: 2000-09-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1939-48 Citation Subset: AIM; IM |
Affiliation:
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Institute of Virology, University of Cologne, Cologne, Germany. s.hess@uni-koeln.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD95
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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:
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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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