Cancer stem cells in cutaneous melanoma

Cutaneous malignant melanoma is unique in that a lesion, as small as 3 mm in diameter, may cause widespread and disseminated disease that is uniformly fatal owing to the extreme resistance to radio- and chemo-therapy. In this article, we review the evidence that the highly malignant character of cutaneous melanoma is due to the existence of cancer stem cells (CSC) that are responsible for tumorigenic growth and clinical relapse following therapy. Although some markers, such as MS4A1, ABCG2 and ABCB5, are repeatedly found, the various and largely nonoverlapping phenotypes of CSC suggest that either different subpopulations of CSC exist, or that melanoma CSC express a phenotype that continuously changes. For this reason, emphasis is given to identification techniques that are independent of the surface phenotype of melanoma CSC. Finally, in view of their efficient efflux of toxic substances, melanoma CSC play a crucial role in the chemoresistance of melanoma, and targeting the CSC is considered to increase the impact of chemotherapy enormously.