Cancer stem cells in uveal melanoma

Abstract

Despite extensive research into uveal melanoma many key questions remain unanswered. These include: (a) when during uveal melanoma development does tumour cell dissemination occur? (b) why do uveal melanoma cells preferentially metastasise to the liver? And (c) how do metastatic uveal melanoma cells resist current therapeutic options? One concept that is helping to address similar questions in other cancers is the hypothesis that a subpopulation of tumour cells possesses biological properties akin to those described for normal tissue stem cells. Data suggest that these so-called "cancer stem cells" undergo self-renewal, drive tumour progression and metastasis, and initiate new tumours even after many years of apparent "dormancy", as well as providing a reservoir of cells resistant to chemotherapy. Only now, however, are researchers developing the necessary in vitro assays and in vivo models to evaluate the self-renewal and tumour-propagation capabilities of isolated uveal melanoma cells. This chapter summarises the current concepts of cancer stem cell biology and discusses evidence for the existence of cancer stem cells in uveal melanoma. Particular attention is paid to embryonic gene signatures and developmental signalling pathways, transdifferentiation capabilities and drug efflux transporters, drawing on comparisons with other cancers.