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Melanoma cells influence the differentiation pattern of human epidermal keratinocytes.

Kodet O, Lacina L, Krejčí E, Dvořánková B, Grim M, Štork J, Kodetová D, Vlček Č, Šáchová J, Kolář M, Strnad H, Smetana K - Mol. Cancer (2015)

Bottom Line: 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.We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro.

View Article: PubMed Central - PubMed

Affiliation: 1st Faculty of Medicine, Institute of Anatomy, Charles University in Prague, U Nemocnice 3, CZ-12800 Prague, Czech Republic. strnad@img.cas.cz.

ABSTRACT

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.

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Melanoma cell activity is in addition to other factors dependent on the activity of tumor infiltrating inflammatory cells and fibroblasts. The melanoma cells are able to influence the differentiation pattern of keratinocytes by production of FGF-2, VEGF-A, IL-8, and CXCL-1. The reciprocal activity of keratinocytes to melanoma cells needs further research.
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Fig6: Melanoma cell activity is in addition to other factors dependent on the activity of tumor infiltrating inflammatory cells and fibroblasts. The melanoma cells are able to influence the differentiation pattern of keratinocytes by production of FGF-2, VEGF-A, IL-8, and CXCL-1. The reciprocal activity of keratinocytes to melanoma cells needs further research.

Mentions: It should be clearly concluded here that melanoma cells are able to influence the phenotype of HPK. This observation is supported by observation of pseudoepitheliomatous hyperplasia of epidermis surrounding nodular melanoma site. Hyperplasia is accompanied by dysregulation of K14 expression in the epithelium. As summarized by Brandber and Haass[10], melanoma microenvironment includes endothelium, inflammatory cells and also keratinocytes. The keratinocytes are clearly involved in crosstalk with malignant melanocytes (Figure 6). Our data support the hypothesis of the importance of microenvironment in melanoma biology, however our understanding to these mechanisms is still limited. Mutual intercellular interactions in melanoma seem to participate in formation of this tumorigenic micromilieu. The potential role of melanoma cell-activated keratinocytes on tumor biology including metastasation shall be verified.Figure 6


Melanoma cells influence the differentiation pattern of human epidermal keratinocytes.

Kodet O, Lacina L, Krejčí E, Dvořánková B, Grim M, Štork J, Kodetová D, Vlček Č, Šáchová J, Kolář M, Strnad H, Smetana K - Mol. Cancer (2015)

Melanoma cell activity is in addition to other factors dependent on the activity of tumor infiltrating inflammatory cells and fibroblasts. The melanoma cells are able to influence the differentiation pattern of keratinocytes by production of FGF-2, VEGF-A, IL-8, and CXCL-1. The reciprocal activity of keratinocytes to melanoma cells needs further research.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4325966&req=5

Fig6: Melanoma cell activity is in addition to other factors dependent on the activity of tumor infiltrating inflammatory cells and fibroblasts. The melanoma cells are able to influence the differentiation pattern of keratinocytes by production of FGF-2, VEGF-A, IL-8, and CXCL-1. The reciprocal activity of keratinocytes to melanoma cells needs further research.
Mentions: It should be clearly concluded here that melanoma cells are able to influence the phenotype of HPK. This observation is supported by observation of pseudoepitheliomatous hyperplasia of epidermis surrounding nodular melanoma site. Hyperplasia is accompanied by dysregulation of K14 expression in the epithelium. As summarized by Brandber and Haass[10], melanoma microenvironment includes endothelium, inflammatory cells and also keratinocytes. The keratinocytes are clearly involved in crosstalk with malignant melanocytes (Figure 6). Our data support the hypothesis of the importance of microenvironment in melanoma biology, however our understanding to these mechanisms is still limited. Mutual intercellular interactions in melanoma seem to participate in formation of this tumorigenic micromilieu. The potential role of melanoma cell-activated keratinocytes on tumor biology including metastasation shall be verified.Figure 6

Bottom Line: 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.We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro.

View Article: PubMed Central - PubMed

Affiliation: 1st Faculty of Medicine, Institute of Anatomy, Charles University in Prague, U Nemocnice 3, CZ-12800 Prague, Czech Republic. strnad@img.cas.cz.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus