title: Upregulation of IL-6, IL-8 and CXCL-1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro: Immunohistochemical and transcriptomic analyses.
abstract: BACKGROUND
  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.
authors.affiliation: Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Academy of Science of the Czech Republic, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Kolář
authors.forename: Pavol
authors.initials: P
authors.lastname: Szabo
authors.forename: Barbora
authors.initials: B
authors.lastname: Dvořánková
authors.forename: Lukáš
authors.initials: L
authors.lastname: Lacina
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.forename: Hynek
authors.initials: H
authors.lastname: Strnad
authors.forename: Jana
authors.initials: J
authors.lastname: Sáchová
authors.forename: Cestmír
authors.initials: C
authors.lastname: Vlček
authors.forename: Jan
authors.initials: J
authors.lastname: Plzák
authors.forename: Martin
authors.initials: M
authors.lastname: Chovanec
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Cada
authors.forename: Jan
authors.initials: J
authors.lastname: Betka
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Fík
authors.forename: Jan
authors.initials: J
authors.lastname: Pačes
authors.forename: Hana
authors.initials: H
authors.lastname: Kovářová
authors.forename: Jan
authors.initials: J
authors.lastname: Motlík
authors.forename: Karla
authors.initials: K
authors.lastname: Jarkovská
authors.forename: Karel
authors.initials: K
authors.lastname: Smetana
mesh_terms: D045744:Cell Line, Tumor; D054360:Chemokine CXCL1 / Q000096:biosynthesis* / Q000235:genetics; D020405:Dermis / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C475829:CXCL1 protein, human; C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D009363:Neoplasm Proteins