A novel fully-humanised 3D skin equivalent to model early melanoma invasion
Authors
Hill DS, Robinson NDP, Caley MP, Chen M, O'Toole EA, Armstrong JL, Przyborski S, Lovat PE
Institution
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
Country
United States
Year
2015
Journal
Molecular Cancer Therapeutics
Abstract
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.