Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase.
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 (ALDH(high)/ALDH(low)) were isolated. ALDH(high) and ALDH(low) populations were implanted into NOD/SCID mice and monitored for tumor development.


RESULTS
ALDH(high) cells represented a small percentage of the tumor cells (1% to 7.8%). ALDH(high) cells formed tumors from as few as 500 cells in 24/45 implantations, whereas only 3/37 implantations of ALDH(low) cells formed tumors.


CONCLUSIONS
ALDH(high) 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.
Clay
Matthew R
MR
Department of Molecular and Cell Biology, University of Wisconsin, Madison, Wisconsin, USA.
Tabor
Mark
M
Owen
John Henry
JH
Carey
Thomas E
TE
Bradford
Carol R
CR
Wolf
Gregory T
GT
Wicha
Max S
MS
Prince
Mark E
ME
D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008875:Middle Aged; D023421:Models, Animal; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D000444:Aldehyde Dehydrogenase