PMID- 10925276
OWN - NLM
STAT- MEDLINE
DCOM- 20000914
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 165
IP  - 4
DP  - 2000 Aug 15
TI  - Loss of IL-6 receptor expression in cervical carcinoma cells inhibits autocrine 
      IL-6 stimulation: abrogation of constitutive monocyte chemoattractant protein-1 
      production.
PG  - 1939-48
AB  - 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.
FAU - Hess, S
AU  - Hess S
AD  - Institute of Virology, University of Cologne, Cologne, Germany. 
      s.hess@uni-koeln.de
FAU - Smola, H
AU  - Smola H
FAU - Sandaradura De Silva, U
AU  - Sandaradura De Silva U
FAU - Hadaschik, D
AU  - Hadaschik D
FAU - Kube, D
AU  - Kube D
FAU - Baldus, S E
AU  - Baldus SE
FAU - Flucke, U
AU  - Flucke U
FAU - Pfister, H
AU  - Pfister H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (fas Receptor)
RN  - 0 (interleukin-6 receptor alpha)
SB  - IM
MH  - Apoptosis/immunology
MH  - Autocrine Communication/*immunology
MH  - Carcinoma in Situ/immunology/metabolism/pathology
MH  - Carcinoma, Squamous Cell/immunology/metabolism/pathology
MH  - Cell Line, Transformed
MH  - Chemokine CCL2/*antagonists & inhibitors/*biosynthesis
MH  - DNA-Binding Proteins/biosynthesis/metabolism
MH  - Female
MH  - Humans
MH  - Interleukin-6/*antagonists & inhibitors/biosynthesis/pharmacology/*physiology
MH  - Receptors, Interleukin-6/antagonists & inhibitors/*biosynthesis/physiology
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/immunology
MH  - Solubility
MH  - Trans-Activators/biosynthesis/metabolism
MH  - Tumor Cells, Cultured
MH  - Uterine Cervical Neoplasms/*immunology/*metabolism/pathology
MH  - fas Receptor/physiology
EDAT- 2000/08/05 11:00
MHDA- 2000/09/19 11:01
CRDT- 2000/08/05 11:00
PHST- 2000/08/05 11:00 [pubmed]
PHST- 2000/09/19 11:01 [medline]
PHST- 2000/08/05 11:00 [entrez]
AID - ji_v165n4p1939 [pii]
AID - 10.4049/jimmunol.165.4.1939 [doi]
PST - ppublish
SO  - J Immunol. 2000 Aug 15;165(4):1939-48. doi: 10.4049/jimmunol.165.4.1939.