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Melanoma cells influence the differentiation pattern of human epidermal keratinocytes
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SYSNO ASEP 0442531 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Melanoma cells influence the differentiation pattern of human epidermal keratinocytes Tvůrce(i) Kodet, O. (CZ)
Lacina, L. (CZ)
Krejčí, E. (CZ)
Dvořáková, B. (CZ)
Grim, M. (CZ)
Štork, J. (CZ)
Kodetová, D. (CZ)
Vlček, Čestmír (UMG-J) RID
Šáchová, Jana (UMG-J)
Kolář, Michal (UMG-J) RID, ORCID
Strnad, Hynek (UMG-J) RID
Smetana, K. (CZ)Zdroj.dok. Molecular Cancer
Roč. 14, č. 1 (2015), s. 1-1Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Melanoma ; Cancer microenvironment ; Melanocyte Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP304/12/1333 GA ČR - Grantová agentura ČR NT13488 GA MZd - Ministerstvo zdravotnictví ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMG-J - RVO:68378050 UT WOS 000349489400001 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2015
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