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Upregulation of IL‐6, IL‐8 and CXCL‐1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro : Immunohistochemical and transcriptomic analyses
Author(s) -
Kolář Michal,
Szabo Pavol,
Dvořánková Barbora,
Lacina Lukáš,
Gabius HansJoachim,
Strnad Hynek,
Šáchová Jana,
Vlček Čestmír,
Plzák Jan,
Chovanec Martin,
Čada Zdeněk,
Betka Jan,
Fík Zdeněk,
Pačes Jan,
Kovářová Hana,
Motlík Jan,
Jarkovská Karla,
Smetana Jr Karel
Publication year - 2012
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/boc.201200018
Subject(s) - chemokine , biology , downregulation and upregulation , fibroblast , cytokine , interleukin 8 , cancer research , wound healing , cell culture , transcriptome , in vitro , microbiology and biotechnology , immunology , pathology , inflammation , gene expression , medicine , gene , biochemistry , genetics
Background information Considering an analogy between wound healing and tumour progression, we studied chemokine and cytokine transcription and expression in normal fibroblasts by co‐culture and in situ . Results Whole‐genome transcriptome profiling revealed strong upregulation for the interleukin (IL)‐6, IL‐8 and the chemokine CXCL‐1 in in vitro co‐cultures of normal fibroblasts with either normal or malignant epithelial cells compared to fibroblast cultures. The same ILs/chemokines were distinctly upregulated in clinical samples of squamous cell carcinoma when compared with paired normal mucosae. Analysis of culture supernatants showed that during the course of co‐culture of the fibroblasts with the epithelial cells, IL‐6, IL‐8 and CXCL‐1 were secreted to the culture medium. Experiments with addition of any of the proteins to the culture medium supported the notion that these ILs/chemokines strongly contributed to maintenance of a low‐differentiation phenotype of epithelial cells, evaluated by the detection of keratin‐8. Simultaneous addition of all factors increased the extent of the effect. These studies were extended by experiments with epithelial cells, either cultured in medium conditioned by preceding use for malignant keratinocytes without and in the presence of normal or cancer‐associated fibroblasts or medium containing antibodies against IL‐6, IL‐8 and CXCL‐1. Conclusions Our results indicate an analogy between wound healing and tumour growth, support the importance of epithelial–mesenchymal interaction in this model system and establish a potential bio‐inspired anticancer therapy.