Melanocytic spheroids as a model for melanoma development and metastasis (2007–2008)
The pigment responsible for skin, hair and eye colour is produced by the mature melanocyte cell that arises from a single source during development of the embryo. Precursor cells known as melanoblasts migrate through the skin and act as future stem cells for the melanocytes. How these cells arise from a latent reservoir of adult stem cells has not been characterised to any extent in human skin, but may derive from specialised cells known as skin-derived precursors (SKP) that have recently been described and which grow as spheres in culture. Tumourigenesis of the melanocyte results in malignant melanoma and it is possible that migratory and other properties of the SKP-melanoblast stem cell are re-enacted in melanoma cells which act in a highly invasive manner. Indeed melanoma cells themselves can be induced to grow as non-adherent multicellular spheres when gown in media used for stem cell growth, and when they do these are known as melanoma spheroid (MS) cells. We intend to study the molecular genetic differences in SKP and MS cells as we induce them to differentiate, and during the melanoblast to the melanocyte transition using cells grown in tissue culture. SKP, melanoblast and melanocyte cell strains will be established from human skin and these cells will provide a resource to investigate the range and role of different growth factors in directing gene expression patterns and UV-sensitivities. Additionally, the role of these growth factors in the variability of individuals to respond to sun-exposure will be studied in cells in culture. Hopefully, this study will provide insight into the molecular mechanism of melanocyte differentiation and aberrant transformation of melanoma cells that can be developed into practical outcomes for future prevention or therapy.