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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.
MedLine Citation:
PMID:  23043537     Owner:  NLM     Status:  Publisher    
BACKGROUND INFORMATION: Considering an analogy between wound healing and tumor progression, we studied chemo- and cytokine expression in normal fibroblasts by coculture and in situ, completed by transcriptome analyses. RESULTS: Whole-genome transcriptome profiling revealed strong upregulation for the interleukins-6 and -8 (IL-6, IL-8) and the chemokine CXCL-1 in in vitro cocultures of normal fibroblasts with either normal or malignant epithelial cells compared to fibroblast cultures. The same interleukins/chemokines were distinctly upregulated in clinical samples of squamous cell carcinoma tissues when compared to paired normal mucosae. Analysis of culture supernatants showed that, during the course of coculture 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 protein from this set of effectors to the culture medium supported the notion that these interleukins/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 tumor growth, support the importance of epithelial-mesenchymal interaction in this experimental system and establish a potential design of a bio-inspired anticancer therapy.
Michal Kolář; Pavol Szabo; Barbora Dvořánková; Lukáš Lacina; Hans-Joachim Gabius; Hynek Strnad; Jana Sáchová; Cestmír Vlček; Jan Plzák; Martin Chovanec; Zdeněk Cada; Jan Betka; Zdeněk Fík; Jan Pačes; Hana Kovářová; Jan Motlík; Karla Jarkovská; Karel Smetana
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-9
Journal Detail:
Title:  Biology of the cell / under the auspices of the European Cell Biology Organization     Volume:  -     ISSN:  1768-322X     ISO Abbreviation:  Biol. Cell     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8108529     Medline TA:  Biol Cell     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France.
Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Academy of Science of the Czech Republic, Prague, Czech Republic.
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