Model Systems for the Study of Malignant Melanoma

Abstract

Since the first resection of melanoma by Hunter in 1787, efforts to treat patients with this deadly malignancy have been ongoing. Initial work to understand melanoma biology for therapeutics development began with the employment of isolated cancer cells grown in cell cultures. However, these models lack in vivo interactions with the tumor microenvironment. Melanoma cell line transplantation into suitable animals such as mice has been informative and useful for testing therapeutics as a preclinical model. Injection of freshly isolated patient melanomas into immunodeficient animals has shown the capacity to retain the genetic heterogeneity of the tumors, which is lost during the long-term culture of melanoma cells. Upon advancement of technology, genetically engineered animals have been generated to study the spontaneous development of melanomas in light of newly discovered genetic aberrations associated with melanoma formation. Culturing melanoma cells in a matrix generate tumor spheroids, providing an in vitro environment that promotes the heterogeneity commonplace with human melanoma and displaces the need for animal care facilities. Advanced 3D cultures have been created simulating the structure and cellularity of human skin to permit in vitro testing of therapeutics on melanomas expressing the same phenotype as demonstrated in vivo. This review will discuss these models and their relevance to the study of melanomagenesis, growth, metastasis, and therapy.

Keywords: B16; BRAF; Genetically engineered mice; Malignant melanoma; NRAS; Tumor spheroids; Ultraviolet light; Xenograft transplantation; YUMM; Zebrafish.