title: ABCB1 identifies a subpopulation of uveal melanoma cells with high metastatic propensity.
abstract: Metastasis of tumor cells to distant organs is the leading cause of death in melanoma. Yet, the mechanisms of metastasis remain poorly understood. One key question is whether all cells in a primary tumor are equally likely to metastasize or whether subpopulations of cells preferentially give rise to metastases. Here, we identified a subpopulation of uveal melanoma cells expressing the multidrug resistance transporter ABCB1 that are highly metastatic compared to ABCB1(-) bulk tumor cells. ABCB1(+) cells also exhibited enhanced clonogenicity, anchorage-independent growth, tumorigenicity and mitochondrial activity compared to ABCB1(-) cells. A375 cutaneous melanoma cells contained a similar subpopulation of highly metastatic ABCB1(+) cells. These findings suggest that some uveal melanoma cells have greater potential for metastasis than others and that a better understanding of such cells may be necessary for more successful therapies for metastatic melanoma.
authors.affiliation: Departments of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA.  Département d'Ophtalmologie, Université Laval, Québec, QC, Canada  Department of Otolaryngology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Solange
authors.initials: S
authors.lastname: Landreville
authors.forename: Olga A
authors.initials: OA
authors.lastname: Agapova
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Kneass
authors.forename: Christian
authors.initials: C
authors.lastname: Salesse
authors.forename: J William
authors.initials: JW
authors.lastname: Harbour
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins