Cellular and molecular biology of human melanoma

Melanoma develops from a series of architectural and phenotypically distinct stages and becomes progressively aggressive culminating in metastasis. Over the years, considerable progress has been made in understanding the biological, pathological and immunological aspects of human melanoma progression. Epidemiological and experimental studies have suggested that intense exposures during early childhood to UV radiation may lead to melanoma in adults, but molecular and genetic studies have revealed few autosomal abnormalities, infrequent mutational spectra and very little epistatic and epigenetic mechanisms. At the cellular level it has become clear that deregulated homeostatic control in the skin microenvironment occurs through alterations in the expression of specific proteins. These include growth factors and their receptors, adhesion molecules and their ligands, proteases and their substrates, and transcription factors and their target genes. Like in most other human tumors, there are alterations in the regulatory networks involving signal transduction in human melanoma. Appropriate models mimicking the human disease have been developed. However, these have not yet led to major advances in delineating the precise molecular determinants responsible for melanoma progression. Results from recent studies have put more impetus on identification of new molecules that promise to become better therapeutic targets. This review focuses on the most recent progress in understanding the molecular determinants of tumor progression with a particular emphasis on melanoma as a biological responder to altered homeostasis.