Melanoma cells influence the differentiation pattern of human epidermal keratinocytes

Molecular Cancer

Research

Barbora Dvořánková¹  Karel Smetana¹  Eliška Krejčí¹  Miloš Grim¹  Ondřej Kodet²  Lukáš Lacina³  Daniela Kodetová⁴  Jiří Štork⁵  Čestmír Vlček⁶  Hynek Strnad⁶  Jana Šáchová⁶  Michal Kolář⁶ 

[1] 1st Faculty of Medicine, Institute of Anatomy, Charles University in Prague, U Nemocnice 3, CZ-12800, Prague, Czech Republic;1st Faculty of Medicine, Institute of Anatomy, Charles University in Prague, U Nemocnice 3, CZ-12800, Prague, Czech Republic;Department of Dermatovenerology, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, U Nemocnice 2, CZ-12800, Prague, Czech Republic;1st Faculty of Medicine, Institute of Anatomy, Charles University in Prague, U Nemocnice 3, CZ-12800, Prague, Czech Republic;Department of Dermatovenerology, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, U Nemocnice 2, CZ-12800, Prague, Czech Republic;Institute of Medical Biology, A*STAR, 8A Biomedical Grove, No. 06-06 Immunos, 138648, Singapore, Singapore;2nd Faculty of Medicine, Institute of Pathology and Molecular Medicine, Charles University in Prague, V Úvalu 84, CZ-15006, Prague, Czech Republic;Department of Dermatovenerology, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, U Nemocnice 2, CZ-12800, Prague, Czech Republic;Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Laboratory of Genomics and Bioinformatics, Vídeňská 1083, CZ-14220, Prague, Czech Republic;

关键词: Melanoma;    Cancer microenvironment;    Melanocyte;    Intercellular interaction;    Pseudoepitheliomatous hyperplasia;   

DOI  :  10.1186/1476-4598-14-1

 received in 2014-07-30, accepted in 2014-12-15,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundNodular 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).MethodsComparative 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.ResultsEpidermis 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.ConclusionWe 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.

【 授权许可】

Unknown   
© Kodet et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.