Abstract An important role for phenotype switching has been demonstrated in metastasis and therapeutic resistance of both melanoma and epithelial tumours. Phenotype switching in epithelial tumours is driven by a minority cancer stem cell sub-population with lineage plasticity, but such a sub-population has not been identified in melanoma. We investigated whether cell surface markers used to identify cancer stem cells in epithelial tumours could help to identify a cancer stem cell sub-population with lineage plasticity in melanoma. We identified a CD24+CD271+ minority sub-population in melanoma that possesses enhanced stem cell characteristics and lineage plasticity. We further found that that, unlike in epithelial tumours, more differentiated sub-populations in melanoma also possessed these attributes to a lesser extent. The CD24+CD271+ stem cell sub-population was observed in only 10% of human melanomas, mainly at the invasive front. The lack of this stem cell sub-population in the majority of human melanoma specimens led us to conclude that it may not be required for melanoma progression. This may be due to the observed diffuse nature of stem cell characteristics in melanoma. However, the enhanced self-renewal, lineage plasticity, invasive ability and drug resistance of the CD24+CD271+ sub-population may signal a contextual requirement for these stem cells when melanomas face challenging environments both in clinical melanoma and in experimental systems.

A CD24+CD271+ melanoma cancer stem cell generates a diffuse hierarchy of attributes that promote metastasis and therapeutic resistance