Melanoma cells influence the differentiation pattern of human epidermal keratinocytes

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• 作者：Ond?ej Kodet (1) (2)
  Luká? Lacina (1) (2) (3)
  Eli?ka Krej?í (1)
  Barbora Dvo?ánková (1)
  Milo? Grim (1)
  Ji?í ?tork (2)
  Daniela Kodetová (4)
  ?estmír Vl?ek (5)
  Jana ?áchová (5)
  Michal Kolá? (5)
  Hynek Strnad (5)
  Karel Smetana (1)
  
  1. 1st Faculty of Medicine ; Institute of Anatomy ; Charles University in Prague ; U Nemocnice 3 ; CZ-12800 ; Prague ; Czech Republic
  2. Department of Dermatovenerology ; Charles University in Prague ; 1st Faculty of Medicine and General University Hospital ; U Nemocnice 2 ; CZ-12800 ; Prague ; Czech Republic
  3. Institute of Medical Biology ; A*STAR ; 8A Biomedical Grove ; No. 06-06 Immunos ; Singapore ; 138648 ; Singapore
  4. 2nd Faculty of Medicine ; Institute of Pathology and Molecular Medicine ; Charles University in Prague ; V úvalu 84 ; CZ-15006 ; Prague ; Czech Republic
  5. 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
• 刊名：Molecular Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：14
• 期：1
• 参考文献：1. Kulesa PM, Kasemeier-Kulesa JC, Teddy JM, Margaryan NV, Seftor EA, Seftor RE, / et al.: Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment. / Proc Natl Acad Sci U S A 2006, 103:3752-757. 10.1073/pnas.0506977103 CrossRef
  2. Hendrix MJ, Seftor EA, Seftor RE, Kasemeier-Kulesa J, Kulesa PM, Postovit LM: Reprogramming metastatic tumour cells with embryonic microenvironments. / Nat Rev Cancer 2007, 7:246-55. 10.1038/nrc2108 CrossRef
  3. Plzak J, Lacina L, Chovanec M, Dvorankova B, Szabo P, Cada Z, / et al.: Epithelial-stromal interaction in squamous cell epithelium-derived tumors: an important new player in the control of tumor biological properties. / Anticancer Res 2010, 30:455-62.
  4. Lacina L, Dvorankova B, Smetana K Jr, Chovanec M, Plzak J, Tachezy R, / et al.: Marker profiling of normal keratinocytes identifies the stroma from squamous cell carcinoma of the oral cavity as a modulatory microenvironment in co-culture. / Int J Radiat Biol 2007, 83:837-48. 10.1080/09553000701694343 CrossRef
  5. Strnad H, Lacina L, Kolar M, Cada Z, Vlcek C, Dvorankova B, / et al.: Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes. / Histochem Cell Biol 2010, 133:201-11. 10.1007/s00418-009-0661-6 CrossRef
  6. Li L, Dragulev B, Zigrino P, Mauch C, Fox JW: The invasive potential of human melanoma cell lines correlates with their ability to alter fibroblast gene expression in vitro and the stromal microenvironment in vivo. / Int J Cancer 2009, 125:1796-804. 10.1002/ijc.24463 CrossRef
  7. Jager MJ, Ly LV, El Filali M, Madigan MC: Macrophages in uveal melanoma and in experimental ocular tumor models: Friends or foes? / Prog Retin Eye Res 2011, 30:129-46. 10.1016/j.preteyeres.2010.11.004 CrossRef
  8. Sieber-Blum M, Grim M, Hu YF, Szeder V: Pluripotent neural crest stem cells in the adult hair follicle. / Dev Dyn 2004, 231:258-69. 10.1002/dvdy.20129 CrossRef
  9. Haass NK, Ripperger D, Wladykowski E, Dawson P, Gimotty PA, Blome C, / et al.: Melanoma progression exhibits a significant impact on connexin expression patterns in the epidermal tumor microenvironment. / Histochem Cell Biol 2010, 133:113-24. 10.1007/s00418-009-0654-5 CrossRef
  10. Brandner JM, Haass NK: Melanoma’s connections to the tumour microenvironment. / Pathology 2013, 45:443-52. 10.1097/PAT.0b013e328363b3bd CrossRef
  11. Krejci E, Grim M: Isolation and characterization of neural crest stem cells from adult human hair follicles. / Folia Biol 2010, 56:149-57.
  12. Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE: Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. / J Cell Biol 1988, 106:761-71. 10.1083/jcb.106.3.761 CrossRef
  13. Dvorankova B, Holikova Z,
• 刊物主题：Cancer Research; Oncology;
• 出版者：BioMed Central
• ISSN：1476-4598

文摘

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--00) 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.