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A novel fully-humanised 3D skin equivalent to model early melanoma invasion.

Hill, D.S. and Robinson, N.D.P. and Caley, M.P. and Chen, M. and O'Toole, E.A. and Armstrong, J.L. and Przyborski, S. and Lovat, P.E. (2015) 'A novel fully-humanised 3D skin equivalent to model early melanoma invasion.', Molecular cancer therapeutics., 14 (11). pp. 2665-2673.


Metastatic melanoma remains incurable, emphasizing the acute need for improved research models to investigate the underlying biologic mechanisms mediating tumor 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 humanized three-dimensional (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 tumor invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates that this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth-phase melanoma invasion.

Item Type:Article
Full text:(AM) Accepted Manuscript
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Date accepted:14 August 2015
Date deposited:02 December 2015
Date of first online publication:01 September 2015
Date first made open access:01 September 2016

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