1. MDR1 expression identifies human melanoma stem cells
- Author
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Itamar Goldstein, Ninette Amariglio, Karen Cesarkas, Gilmor Keshet, Orit Itzhaki, Liraz Shenhav, Arkadi Yakirevitch, Avraham J. Treves, Gideon Rechavi, and Jacob Schachter
- Subjects
Homeobox protein NANOG ,ATP Binding Cassette Transporter, Subfamily B ,Cellular differentiation ,Biophysics ,Biology ,Stem cell marker ,physiological processes ,Biochemistry ,Cancer stem cell ,Tumor Cells, Cultured ,polycyclic compounds ,Humans ,Telomerase reverse transcriptase ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Melanoma ,Telomerase ,neoplasms ,Molecular Biology ,Homeodomain Proteins ,Induced stem cells ,Membrane Transport Proteins ,ABCB5 ,Nanog Homeobox Protein ,Cell Biology ,Molecular biology ,Multidrug Resistance-Associated Protein 2 ,Cell biology ,DNA-Binding Proteins ,Neoplastic Stem Cells ,Multidrug Resistance-Associated Proteins ,Stem cell - 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.
- Published
- 2008
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