Establishing Human Skin Grafts in Mice as Model for Melanoma Progression

Technological advances often dictate progress in cancer research. Melanoma research has been considerably influenced by implementation of novel techniques and has contributed to our understanding of the mechanism of tumor progression. The three-dimensional (3D) human skin reconstruct is an ideal model to dissect each step of melanoma development and progression. Reconstructed human skin consists of fibroblast-contracted collagen gels as a dermal compartment and a stratified epidermal compartment. The epidermis comprises keratinocytes and normal melanocytes or melanoma cells from different stages. Normal melanocytes in skin reconstructs remain singly distributed at the basement membrane within the basal layer of keratinocytes. The radial growth phase (RGP) melanoma cells grow as cell clusters in the epidermis. The vertical growth phase (VGP) melanoma cells invade the dermis of reconstructs. Metastatic melanoma cells aggressively invade deep into the dermis. Grafting melanoma skin reconstructs onto mice induces local tumor formation and metastatic foci in distant organs such as lungs. The growth patterns and the range of metastases reflect proliferation and metastatic capacity of the original tumors. Skin reconstruct as xenografts enable us to observe to which organs melanoma cells spread. In this chapter, we describe the usefulness of the model in studying not only melanocyte physiology but also pathophysiological conditions such as melanocyte transformation and melanoma progression. A better understanding of these processes will benefit the entire melanoma field.