Human melanoma phenotypes and HERV-K expression

Melanoma development is a multistep process arising from a series of genetic and epigenetic events that includes cell transformation and the change in the interactions between the transformed cells and the host. Despite the clearly defined sequential stages involved in the progression from melanocytes to malignant melanoma, little is known about the events leading to melanoma insurgence and progression. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. In this study we show that melanoma cells in vitro spontaneusly gave rise to a more malignant non-adherent phenotype, characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, features that typically characterize highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus-K (HERV-K) expression and a massive production of viral-like particles, suggesting a tight correlation between HERV replication and melanoma progression.