Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade

M R Loebinger, A Giangreco, K R Groot, L Prichard, K Allen, C Simpson, L Bazley, N Navani, S Tibrewal, D Davies, S M Janes

Research output: Contribution to journalArticlepeer-review

108 Citations (Scopus)

Abstract

Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we performed Hoechst dye efflux assays using four independent cell lines. Results revealed the presence of a rare, drug effluxing stem cell-like side population (SP) of cells within all cell lines tested (SCC-SP cells). These cells resembled previously characterised epithelial stem cells, and SCC-SP cell abundance was positively correlated with overall cellular density and individual cell quiescence. Serial SCC-SP fractionation and passaging increased their relative abundance within the total cell population. Purified SCC-SP cells also exhibited increased clonogenic potential in secondary cultures and enhanced tumorigenicity in vivo. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies.

Original languageEnglish
Pages (from-to)380-7
Number of pages8
JournalBritish Journal of Cancer
Volume98
Issue number2
DOIs
Publication statusPrint publication - 29 Jan 2008
Externally publishedYes

Keywords

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters/antagonists & inhibitors
  • Animals
  • Antineoplastic Agents/pharmacology
  • Biomarkers, Tumor/metabolism
  • Carcinoma, Squamous Cell/genetics
  • Cell Count
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Separation
  • Drug Resistance, Neoplasm/drug effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Multidrug Resistance-Associated Proteins/genetics
  • Neoplasm Proteins/genetics
  • Neoplastic Stem Cells/drug effects
  • Verapamil/pharmacology
  • Xenograft Model Antitumor Assays

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