Upregulation of IL-6, IL-8 and CXCL-1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro: Immunohistochemical and transcriptomic analyses

0387297 - ÚMG 2013 RIV FR eng J - Journal Article
Kolář, Michal - Szabo, Pavol - Dvořánková, Barbora - Lacina, L. - Gabius, H.J. - Strnad, Hynek - Šáchová, Jana - Vlček, Čestmír - Plzák, J. - Chovanec, M. - Čada, Z. - Betka, J. - Fík, Z. - Pačes, Jan - Kovářová, Hana - Motlík, Jan - Jarkovská, Karla - Smetana, K.
Upregulation of IL-6, IL-8 and CXCL-1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro: Immunohistochemical and transcriptomic analyses.
Biology of the Cell. Roč. 104, č. 12 (2012), s. 738-751. ISSN 0248-4900. E-ISSN 1768-322X
R&D Projects: GA MZd(CZ) NT13488
Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50450515
Keywords : CXCL-1 * IL-6 * IL-8 * squamous cell carcinoma * wound healing
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.488, year: 2012

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. 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. Our results indicate an analogy between wound healing and tumour growth, support the importance of epithelialmesenchymal interaction in this model system and establish a potential bio-inspired anticancer therapy.
Permanent Link: http://hdl.handle.net/11104/0218710