Characterization of Human Melanoma Skin Cancer Models: Paving the Way for Model-Based Melanoma Research and Drug Discovery
The need for advanced tissue models in medical research and drug development is more critical than ever. Recent changes in EU law to reduce animal testing and U.S. regulation allowing the FDA to approve drugs without animal trials highlight the importance of these models in advancement of medical science. For the models to be applicable in preclinical studies, it is essential that models are thoroughly characterized so as to understand their applicability and limitations to avoid misinterpretation caused by their limited replication of the biological functions.  In this study, we applied bioimaging and RNA sequencing to assess and contrast the architecture and gene expression profiles of various skin models, including melanoma skin models. Our results indicate that these models closely emulate actual skin morphology and gene expression, with the full-thickness (FT) models exhibiting superior resemblance to human skin, especially in the formation of the basement membrane and cellular interactions. These characteristics make the FT model particularly useful for research that focuses on these aspects. Furthermore, the integrity of the skin-like properties and genetic signatures, of both skin and melanoma cell lines, was maintained upon integration of melanoma cells, establishing these models as robust platforms for cancer research and pharmacological development. The responsiveness of the FT melanoma models to vemurafenib was successfully monitored through live imaging, demonstrating their validity as a reliable, reproducible, and humane tool for cancer research and drug development. Overall design: We investigated gene expression in various artificially grown skin models, including melanoma skin models. These models include epidermis, dermis, full-thickness (containing both epidermis and dermis), melanoma full-thickness models (with melanoma spheroids grown from both the A375 and SK-MEL-28 cell lines).