Original ArticlesThe repopulating cancer cells in melanoma are characterized by increased mitochondrial membrane potential

- B16-F10 melanoma cells have mitochondrial heterogeneity under stress conditions.
- B16-F10 melanoma cells with enhanced mitochondrial membrane potential more efficiently drive tumor formation.
- Enhanced mitochondrial membrane potential may be a marker for cancer-initiating cells and be used to isolate the live cancer-initiating cells.

Although considerable effort has been expended in identifying definitive markers for cancer stem cells (CSCs) or cancer-initiating cells (CICs), the phenotypic plasticity of these cells obviates simple characterization using cell surface markers. We hypothesized that these cells could be characterized by their metabolic properties because they are in a quiescent state with low energy needs. We examined whether cancer cells differ in mitochondrial membrane potential (Δψm) when they are under stress. The Δψm of B16-F10 melanoma cells increased when they were exposed in vitro to serum starvation and chemotherapeutic agents, but not when exposed to hypoxia. Such TMREhigh cells were also present in tumor tissue. They primarily used glucose and/or lactate, and were superior to TMRElow B16-F10 cells in their ability to drive tumor growth. These findings suggest that CSCs or CICs could be identified in heterogeneous melanoma populations by measuring Δψm.