Tumor-produced, active Interleukin-1 β regulates gene expression in carcinoma-associated fibroblasts

József Dudás, Alexandra Fullár, Mario Bitsche, Volker Schartinger, I. Kovalszky, Georg Mathias Sprinzl, Herbert Riechelmann

Research output: Contribution to journalArticle

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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-1β (IL1-β) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-β 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-β processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-β. IL1-β signaling was investigated by western blot and immunocytochemistry. IL1-β-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16. kD active IL1-β, 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 NFκBα. 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-β 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-β-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-β in the tumor cells leads to IL1-β-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression.

Original languageEnglish
Pages (from-to)2222-2229
Number of pages8
JournalExperimental Cell Research
Volume317
Issue number15
DOIs
Publication statusPublished - Sep 10 2011

Fingerprint

Interleukin-1
Fibroblasts
Periodontal Ligament
Carcinoma
Gene Expression
Coculture Techniques
Neoplasms
Interleukin-6
Interleukin-1 Receptors
Dexamethasone
Interleukin-1 Receptor-Associated Kinases
Interferon Regulatory Factor-1
Epithelial-Mesenchymal Transition
Prostaglandin-Endoperoxide Synthases
Tongue
Genes
Squamous Cell Carcinoma
Up-Regulation
Western Blotting
Immunohistochemistry

Keywords

  • Carcinoma-associated fibroblasts (CAFs)
  • Interferon regulatory factor 1 (IRF1)
  • Interleukin-1 receptor-associated kinase-1 (IRAK-1)
  • Interleukin-6 (IL-6)
  • Nuclear factor kappa beta (NFκBα)
  • Prostaglandin-endoperoxide synthase 2 (COX-2)

ASJC Scopus subject areas

  • Cell Biology

Cite this

Tumor-produced, active Interleukin-1 β regulates gene expression in carcinoma-associated fibroblasts. / Dudás, József; Fullár, Alexandra; Bitsche, Mario; Schartinger, Volker; Kovalszky, I.; Sprinzl, Georg Mathias; Riechelmann, Herbert.

In: Experimental Cell Research, Vol. 317, No. 15, 10.09.2011, p. 2222-2229.

Research output: Contribution to journalArticle

Dudás, J, Fullár, A, Bitsche, M, Schartinger, V, Kovalszky, I, Sprinzl, GM & Riechelmann, H 2011, 'Tumor-produced, active Interleukin-1 β regulates gene expression in carcinoma-associated fibroblasts', Experimental Cell Research, vol. 317, no. 15, pp. 2222-2229. https://doi.org/10.1016/j.yexcr.2011.05.023
Dudás, József ; Fullár, Alexandra ; Bitsche, Mario ; Schartinger, Volker ; Kovalszky, I. ; Sprinzl, Georg Mathias ; Riechelmann, Herbert. / Tumor-produced, active Interleukin-1 β regulates gene expression in carcinoma-associated fibroblasts. In: Experimental Cell Research. 2011 ; Vol. 317, No. 15. pp. 2222-2229.
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