A Novel Fully Humanized 3D Skin Equivalent to Model Early Melanoma Invasion.
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.
Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
David S
DS
Hill
School of Biological and Biomedical Sciences, Durham University, Durham, United Kingdom.
Neil D P
ND
Robinson
Centre for Cutaneous Research, Barts and the London SMD, Queen Mary University of London, Blizard Institute, London, United Kingdom.
Matthew P
MP
Caley
Norris Comprehensive Cancer Centre, University of Southern California, Los Angeles, California.
Mei
M
Chen
Centre for Cutaneous Research, Barts and the London SMD, Queen Mary University of London, Blizard Institute, London, United Kingdom.
Edel A
EA
O'Toole
Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom. Faculty of Applied Sciences, University of Sunderland, Sunderland, United Kingdom.
Jane L
JL
Armstrong
School of Biological and Biomedical Sciences, Durham University, Durham, United Kingdom. penny.lovat@ncl.ac.uk stefan.przyborski@durham.ac.uk.
Stefan
S
Przyborski
Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, United Kingdom. penny.lovat@ncl.ac.uk stefan.przyborski@durham.ac.uk.
Penny E
PE
Lovat
D016475:3T3 Cells; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058965:MART-1 Antigen / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D017768:Skin, Artificial; D059016:Tumor Microenvironment
D014408:Biomarkers, Tumor; D058965:MART-1 Antigen