title: MDR1 expression identifies human melanoma stem cells.
abstract: ABC transporters are often found to be inherently expressed in a wide variety of stem cells, where they provide improved protection from toxins. We found a subpopulation of human melanoma cells expressing multidrug-resistance gene product 1 (MDR1). This fraction co-expresses the ABC transporters, ABCB5 and ABCC2 in addition to the stem cell markers, nanog and human telomerase reverse transcriptase (hTERT). The clonogenicity and self-renewal capacity of MDR1(+) melanoma cells were investigated in single cell settings using the limiting dilution assay. We found that the MDR1(+) cells, isolated by FACS sorting, demonstrated a higher self-renewal capacity than the MDR1(-) fraction, a key stem cell feature. Moreover, MDR1(+) cells had higher ability to form spheres in low attachment conditions, a hallmark of cancer. In conclusion, these novel findings imply that the MDR1(+) cells represent melanoma stem cells and thus should be considered as a unique cellular target for future anti-melanoma therapies.
authors.affiliation: Cancer Research Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University Tel Aviv, 52621, Israel.
authors.forename: Gilmor I
authors.initials: GI
authors.lastname: Keshet
authors.forename: Itamar
authors.initials: I
authors.lastname: Goldstein
authors.forename: Orit
authors.initials: O
authors.lastname: Itzhaki
authors.forename: Karen
authors.initials: K
authors.lastname: Cesarkas
authors.forename: Liraz
authors.initials: L
authors.lastname: Shenhav
authors.forename: Arkadi
authors.initials: A
authors.lastname: Yakirevitch
authors.forename: Avraham J
authors.initials: AJ
authors.lastname: Treves
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D019098:Telomerase / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000071317:Nanog Homeobox Protein; D019098:Telomerase; C513055:ABCB1 protein, human; C480744:ABCB5 protein, human; C000715087:ABCC2 protein, human; C486780:NANOG protein, human