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 language | English |
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Pages (from-to) | 380-7 |
Number of pages | 8 |
Journal | British Journal of Cancer |
Volume | 98 |
Issue number | 2 |
DOIs | |
Publication status | Print publication - 29 Jan 2008 |
Externally published | Yes |
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