Human xenografts, human skin and skin reconstructs for studies in melanomadevelopment and progression

Melanoma develops from a series of architectural and phenotypically distinc t stages and becomes progressively aggressive. Considerable progress has be en made in understanding the biological, pathological, and immunological as pects of human melanoma. Genetic and cytogenetic studies have revealed broa d chromosomal abnormalities and wide mutational spectra. Precise biological and molecular determinants responsible for melanoma progression are not ye t known. This is in part due to lack of experimental models that mimic huma n melanomas. Experimental models in melanoma should not only identify cause and origin of malignancy, but also should represent the ordered progressio n steps that culminate in metastasis to distant organs. Currently, there ar e several mouse and other vertebrate melanoma models under investigation; s everal of them promise to shed light on mechanisms of melanomagenesis. Howe ver, many of them suffer from lack of context to human skin architecture an d hence, are of basic interest. The lack of appropriate models impeded the efforts to understand origin, etiology, progression and ultimately therapeu tic benefits to humans. Development of human skin-mouse chimeric models has appeal because it mimics human diseases. In addition, human artificial ski n constructs in vitro promises to be a versatile and efficient model to stu dy not only origin and mechanisms of melanoma, but also progression. This r eview will focus on the recent progress in establishing tumor models in mel anoma in general and their relevance to human melanoma as molecular determi nants of tumor progression.