MDR1 expression identifies human melanoma stem cells

  • Keshet G
  • Goldstein I
  • Itzhaki O
 et al. 
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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. © 2008 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Anchorage independence
  • Cancer stem cells
  • Melanoma
  • Multidrug resistance
  • Self-renewal

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  • Gilmor I. Keshet

  • Itamar Goldstein

  • Orit Itzhaki

  • Karen Cesarkas

  • Liraz Shenhav

  • Arkadi Yakirevitch

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