The in vitro spheroid melanoma cell culture assay: cues on tumor initiation?

Cancer stem cells (CSCs) represent malignant subpopulations that initiate and maintain tumorigenic growth in hierarchically organized tumors via their considerable capacity for self-renewal and differentiation. CSCs have been identified in several human malignancies, including human malignant melanoma. Perego and colleagues' report in this issue indicates that CSCs capable of melanoma initiation in serial human-to-mouse xenotransplantation assays may be contained both among spheroid melanoma cell cultures (melanospheres) and among adherent melanoma cultures upon in vitro expansion. These results challenge the utility of the melanosphere assay as a surrogate tool for CSC identification in human melanomas and underline the importance of molecularly defined malignant melanoma initiating cells for CSC-focused diagnostic and therapeutic investigations.