MDR1 expression identifies human melanoma stem cells

Gilmor I. Keshet*, Itamar Goldstein, Orit Itzhaki, Karen Cesarkas, Liraz Shenhav, Arkadi Yakirevitch, Avraham J. Treves, Jacob Schachter, Ninette Amariglio, Gideon Rechavi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

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.

Original languageEnglish
Pages (from-to)930-936
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume368
Issue number4
DOIs
StatePublished - 18 Apr 2008

Keywords

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

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