Human xenografts, human skin and skin reconstructs for studies in melanoma development and progression.

Abstract

Melanoma develops from a series of architectural and phenotypically distinct stages and becomes progressively aggressive. Considerable progress has been made in understanding the biological, pathological, and immunological aspects of human melanoma. Genetic and cytogenetic studies have revealed broad chromosomal abnormalities and wide mutational spectra. Precise biological and molecular determinants responsible for melanoma progression are not yet known. This is in part due to lack of experimental models that mimic human melanomas. Experimental models in melanoma should not only identify cause and origin of malignancy, but also should represent the ordered progression steps that culminate in metastasis to distant organs. Currently, there are several mouse and other vertebrate melanoma models under investigation; several of them promise to shed light on mechanisms of melanomagenesis. However, many of them suffer from lack of context to human skin architecture and hence, are of basic interest. The lack of appropriate models impeded the efforts to understand origin, etiology, progression and ultimately therapeutic benefits to humans. Development of human skin-mouse chimeric models has appeal because it mimics human diseases. In addition, human artificial skin constructs in vitro promises to be a versatile and efficient model to study not only origin and mechanisms of melanoma, but also progression. This review will focus on the recent progress in establishing tumor models in melanoma in general and their relevance to human melanoma as molecular determinants of tumor progression.