Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase

• Published in: Head & neck Vol. 32; no. 9; pp. 1195 - 1201
• Main Authors: Clay, Matthew R., Tabor, Mark, Owen, John Henry, Carey, Thomas E., Bradford, Carol R., Wolf, Gregory T., Wicha, Max S., Prince, Mark E.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-09-2010
• Subjects: Aged; Aldehyde dehydrogenase; Aldehyde Dehydrogenase - analysis; Aldehyde Dehydrogenase - metabolism; Animals; Biomarkers, Tumor - analysis; cancer stem cells; Carcinoma, Squamous Cell - pathology; CD44 antigen; Cell Line, Tumor; Cell Separation; Cell Survival; Female; Flow Cytometry; Head; Head and neck cancer; Head and Neck Neoplasms - pathology; Humans; Male; Mice; Mice, Inbred NOD; Middle Aged; Models, Animal; Neck; Neoplastic Stem Cells - pathology; Sensitivity and Specificity; squamous cell cancer; squamous cell carcinoma; Stem cells; Tumor cells; Tumors
• ISSN: 1043-3074; 1097-0347; 1097-0347
• DOI: 10.1002/hed.21315

Background
In accord with the cancer stem cell (CSC) theory, only a small subset of cancer cells are capable of forming tumors. We previously reported that CD44 isolates tumorigenic cells from head and neck squamous cell cancer (HNSCC). Recent studies indicate that aldehyde dehydrogenase (ALDH) activity may represent a more specific marker of CSCs.
Methods
Six primary HNSCCs were collected. Cells with high and low ALDH activity (ALDHhigh/ALDHlow) were isolated. ALDHhigh and ALDHlow populations were implanted into NOD/SCID mice and monitored for tumor development.
Results
ALDHhigh cells represented a small percentage of the tumor cells (1% to 7.8%). ALDHhigh cells formed tumors from as few as 500 cells in 24/45 implantations, whereas only 3/37 implantations of ALDHlow cells formed tumors.
Conclusions
ALDHhigh cells comprise a subpopulation cells in HNSCCs that are tumorigenic and capable of producing tumors at very low numbers. This finding indicates that ALDH activity on its own is a highly selective marker for CSCs in HNSCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2010