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

2008; Springer Nature; Volume: 98; Issue: 2 Linguagem: Inglês

10.1038/sj.bjc.6604185

1532-1827

Michael R. Loebinger, Adam Giangreco, Karen R. Groot, Lisa Prichard, Kirsty Allen, Catherine Simpson, Laura Bazley, Neal Navani, Sapna Tibrewal, Derek Davies, Sam M. Janes,

Renal and related cancers

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.