The repopulating cancer cells in melanoma are characterized by increased mitochondrial membrane potential.
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 TMREhighcells were also present in tumor tissue. They primarily used glucose and/or lactate, and were superior to TMRElowB16-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.
T Cell Therapy Unit, Eutilex Research Institute of Biomedicine, 222 Banpo-daero, Seocho-gu, Seoul, Republic of Korea; Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Republic of Korea; Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
Don G
DG
Lee
Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Republic of Korea.
Beom K
BK
Choi
T Cell Therapy Unit, Eutilex Research Institute of Biomedicine, 222 Banpo-daero, Seocho-gu, Seoul, Republic of Korea; Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Republic of Korea.
Young H
YH
Kim
T Cell Therapy Unit, Eutilex Research Institute of Biomedicine, 222 Banpo-daero, Seocho-gu, Seoul, Republic of Korea; Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Republic of Korea; Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
Ho S
HS
Oh
Cancer Immunology Branch, Division of Cancer Biology, National Cancer Center, Goyang, Republic of Korea; Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
Sang H
SH
Park
Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
Young Soo
YS
Bae
T Cell Therapy Unit, Eutilex Research Institute of Biomedicine, 222 Banpo-daero, Seocho-gu, Seoul, Republic of Korea; Section of Clinical Immunology, Allergy, and Rheumatology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA. Electronic address: bskwon@eutilex.com.
Byoung S
BS
Kwon
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden; D059016:Tumor Microenvironment
D000970:Antineoplastic Agents; D019344:Lactic Acid; D005947:Glucose; D002945:Cisplatin
Chemotherapeutics; Melanoma; Metabolism; Mitochondrial membrane potential; Repopulating cancer cells