Melanoma-derived induced pluripotent stem cells

Abstract Melanoma, a lethal malignancy of pigment-producing melanocytes, manifests in a variety of clinico-pathologically distinct and molecular subtypes in sun-exposed and nonsun-exposed areas. Melanocytes, which are derived from multipotent neural crest, are present in diverse anatomical locations including eyes and various mucosal membranes. Melanocyte stem cells and melanocyte precursors are also present in other tissues. Elegant studies using genetic mouse models have shown that melanoma can arise from either melanocyte stem cells or differentiated melanocytes depending on the tissue context and oncogenic stimulus. This raises the possibility that different subtypes (and even subsets within each subtype) of human cutaneous melanoma may also reflect distinct cell of origin of these subtypes. Interestingly, phenotypic plasticity, including transdifferention along with vascular and neural lineages, in a subset of human melanomas has been documented and stem cell–like gene expression has also been associated with development of melanoma drug resistance. In this context, reprogramming of melanoma cells to induced pluripotent stem cells (iPSCs) is proving to be a promising strategy to investigate cell or origin and phenotypic and molecular plasticity of human cutaneous melanoma. This chapter provides a comprehensive review of current state of knowledge and the promise of iPSC in unraveling cell of origin of melanoma and as a model to understand melanoma drug resistance mechanisms.