A CD24+CD271+ Melanoma Cancer Stem Cell Possesses Hybrid Characteristics of its Single Marker Counterparts and Promotes Invasion and Therapeutic Resistance

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 identify a cancer stem cell sub-population with lineage plasticity in melanoma. We identified a CD24+CD271+ minority sub-population in melanoma that possesses the stem cell characteristics of lineage plasticity and self-renewal. This population displayed hybrid characteristics, combining the attributes of discrete CD24+ and CD271+ cellular sub-populations but with heightened sphere formation, lineage plasticity, migratory ability and drug resistance over its single-marker counterparts. CD24+ and CD24+CD271+ stem cell sub-populations were observed in 10% of human melanomas, mainly at the invasive front. The lack of CD24+ and CD24+CD271+ stem cells in the majority of human melanoma specimens led us to conclude that they may be dispensable for melanoma progression. Nevertheless, the enhanced sphere formation, lineage plasticity, migratory 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 clinically and in experimental systems.