BACKGROUND: Nodular melanoma is one of the most life threatening tumors with still poor therapeutic outcome. Similarly to other tumors, permissive microenvironment is essential for melanoma progression. Features of this microenvironment are arising from molecular crosstalk between the melanoma cells (MC) and the surrounding cell populations in the context of skin tissue. Here, we study the effect of melanoma cells on human primary keratinocytes (HPK). Presence of MC is as an important modulator of the tumor microenvironment and we compare it to the effect of nonmalignant lowly differentiated cells also originating from neural crest (NCSC). METHODS: Comparative morphometrical and immunohistochemical analysis of epidermis surrounding nodular melanoma (n = 100) was performed. Data were compared to results of transcriptome profiling of in vitro models, in which HPK were co-cultured with MC, normal human melanocytes, and NCSC, respectively. Differentially expressed candidate genes were verified by RT-qPCR. Biological activity of candidate proteins was assessed on cultured HPK. RESULTS: Epidermis surrounding nodular melanoma exhibits hyperplastic features in 90% of cases. This hyperplastic region exhibits aberrant suprabasal expression of keratin 14 accompanied by loss of keratin 10. We observe that MC and NCSC are able to increase expression of keratins 8, 14, 19, and vimentin in the co-cultured HPK. This in vitro finding partially correlates with pseudoepitheliomatous hyperplasia observed in melanoma biopsies. We provide evidence of FGF-2, CXCL-1, IL-8, and VEGF-A participation in the activity of melanoma cells on keratinocytes. CONCLUSION: We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro. This interaction further highlights the role of intercellular interactions in melanoma. The reciprocal role of activated keratinocytes on biology of melanoma cells shall be verified in the future.

• MeSH
• buněčná diferenciace * genetika   MeSH
• chemokin CXCL1 farmakologie   MeSH
• dospělí MeSH
• epidermální buňky * MeSH
• epidermis patologie   MeSH
• fibroblastový růstový faktor 2 farmakologie   MeSH
• interleukin-8 farmakologie   MeSH
• keratin-10 metabolismus   MeSH
• keratin-14 metabolismus   MeSH
• keratinocyty cytologie   účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanocyty metabolismus   MeSH
• melanom metabolismus   patologie   MeSH
• metastázy nádorů MeSH
• mezibuněčná komunikace * MeSH
• nádorové buněčné linie MeSH
• proteiny S100 metabolismus   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• vaskulární endoteliální růstový faktor A farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokin CXCL1 MeSH
• fibroblastový růstový faktor 2 MeSH
• interleukin-8 MeSH
• keratin-10 MeSH
• keratin-14 MeSH
• proteiny S100 MeSH
• vaskulární endoteliální růstový faktor A MeSH