A novel fully-humanised 3D skin equivalent to model early melanoma invasion
Hill DS, Robinson NDP, Caley MP, Chen M, O'Toole EA, Armstrong JL, Przyborski S, Lovat PE
Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK School of Biological and Biomedical Sciences, Durham University, Durham, UK Centre for Cutaneous Research, Barts and the London SMD, Queen Mary University of London, Blizard Institute, London, UK Norris Comprehensive Cancer Centre, University of Southern California, Los Angeles, CA, USA Faculty of Applied Sciences, University of Sunderland, Sunderland, UK
United States
Molecular Cancer Therapeutics
Metastatic melanoma remains incurable, emphasising the acute need for improved research models to investigate the underlying biological mechanisms mediating tumour invasion and metastasis, and to develop more effective targeted therapies to improve clinical outcome. Available animal models of melanoma do not accurately reflect human disease and current in vitro human skin equivalent models incorporating melanoma cells are not fully representative of the human skin microenvironment. We have developed a robust and reproducible, fully-humanised 3D skin equivalent comprising a stratified, terminally differentiated epidermis and a dermal compartment consisting of fibroblast-generated extracellular matrix. Melanoma cells incorporated into the epidermis were able to invade through the basement membrane and into the dermis, mirroring early tumour invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth phase melanoma invasion.
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