title: Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized.
abstract: We investigated whether melanoma is hierarchically organized into phenotypically distinct subpopulations of tumorigenic and nontumorigenic cells or whether most melanoma cells retain tumorigenic capacity, irrespective of their phenotype. We found 28% of single melanoma cells obtained directly from patients formed tumors in NOD/SCID IL2Rγ(null) mice. All stage II, III, and IV melanomas obtained directly from patients had common tumorigenic cells. All tumorigenic cells appeared to have unlimited tumorigenic capacity on serial transplantation. We were unable to find any large subpopulation of melanoma cells that lacked tumorigenic potential. None of 22 heterogeneously expressed markers, including CD271 and ABCB5, enriched tumorigenic cells. Some melanomas metastasized in mice, irrespective of whether they arose from CD271(-) or CD271(+) cells. Many markers appeared to be reversibly expressed by tumorigenic melanoma cells.
authors.affiliation: Howard Hughes Medical Institute.
authors.forename: Elsa
authors.initials: E
authors.lastname: Quintana
authors.forename: Mark
authors.initials: M
authors.lastname: Shackleton
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Foster
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Fullen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sabel
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Johnson
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000068816:Adapalene; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009281:Naphthalenes / Q000378:metabolism; D009362:Neoplasm Metastasis; D010641:Phenotype; D014183:Transplantation, Heterologous / Q000473:pathology
chemical_list: C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D009281:Naphthalenes; D000068816:Adapalene