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Title: Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

Abstract

Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved bymore » DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the presence of SCC-25 tumor cells. IL1-{beta} receptor expression in fibroblasts, especially in CAFs represents a major option in coordination of fibroblast and tumor behavior. A key event in IL1-{beta} signaling, the phosphorylation of IRAK1, occurred in co-cultured fibroblasts, which has lead to nuclear translocation of NF{kappa}B{alpha}, and finally to induction of several genes, including BDNF, IRF1, IL-6 and COX-2. The most enhanced induction was found for IL-6 and COX-2.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [1]
  1. Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)
  2. 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary)
Publication Date:
OSTI Identifier:
22212169
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 317; Journal Issue: 15; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BRAIN; CARCINOMAS; DEXAMETHASONE; FIBROBLASTS; GENES; HEAD; INTERFERON; LIGAMENTS; NECK; PHOSPHORYLATION; PLASMINOGEN; PROSTAGLANDINS; RECEPTORS; TROPOMYOSIN; TUMOR CELLS

Citation Formats

Dudas, Jozsef, Fullar, Alexandra, 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest, Bitsche, Mario, Schartinger, Volker, Kovalszky, Ilona, Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at, and Riechelmann, Herbert. Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts. United States: N. p., 2011. Web. doi:10.1016/J.YEXCR.2011.05.023.
Dudas, Jozsef, Fullar, Alexandra, 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest, Bitsche, Mario, Schartinger, Volker, Kovalszky, Ilona, Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at, & Riechelmann, Herbert. Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts. United States. https://doi.org/10.1016/J.YEXCR.2011.05.023
Dudas, Jozsef, Fullar, Alexandra, 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest, Bitsche, Mario, Schartinger, Volker, Kovalszky, Ilona, Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at, and Riechelmann, Herbert. 2011. "Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts". United States. https://doi.org/10.1016/J.YEXCR.2011.05.023.
@article{osti_22212169,
title = {Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts},
author = {Dudas, Jozsef and Fullar, Alexandra and 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest and Bitsche, Mario and Schartinger, Volker and Kovalszky, Ilona and Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at and Riechelmann, Herbert},
abstractNote = {Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the presence of SCC-25 tumor cells. IL1-{beta} receptor expression in fibroblasts, especially in CAFs represents a major option in coordination of fibroblast and tumor behavior. A key event in IL1-{beta} signaling, the phosphorylation of IRAK1, occurred in co-cultured fibroblasts, which has lead to nuclear translocation of NF{kappa}B{alpha}, and finally to induction of several genes, including BDNF, IRF1, IL-6 and COX-2. The most enhanced induction was found for IL-6 and COX-2.},
doi = {10.1016/J.YEXCR.2011.05.023},
url = {https://www.osti.gov/biblio/22212169}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 15,
volume = 317,
place = {United States},
year = {Sat Sep 10 00:00:00 EDT 2011},
month = {Sat Sep 10 00:00:00 EDT 2011}
}