Cancer stem-like cells (CSCs) play important roles in cancer initiation and progression. CSCs have been isolated using several markers, but those for thyroid CSCs remain to be confirmed. We therefore conducted a comprehensive search for thyroid CSC markers. Expression of nine cell surface markers (CD13, CD15, CD24, CD44, CD90, CD117, CD133, CD166, and CD326) and aldehyde dehydrogenase (ALDH) activity, which are CSC markers in various solid cancers, and the ability to form spheres
in vitro and tumors
in vivo were investigated using eight thyroid cancer cell lines (FRO, KTC1/2/3, TPC1, WRO, ACT1, and 8505C). Among these, four cell lines (FRO, KTC3, ACT1, and 8505C) possessed the both abilities; however, common markers indicative of CSCs were not observed. The pattern of ability to form spheres was completely matched to that of tumor formation, suggesting that our sphere assay is valuable for assessment of tumor-forming ability. Next, the cells were sorted using these markers and subjected to the sphere assay. In three cell lines (FRO, KTC3, and ACT1), ALDH
pos cells showed higher sphere forming ability than ALDH
neg cells but not in other cells. CD326
hi also appeared to be a candidate marker only in FRO cells. However, these subpopulations did not follow a classical hierarchical model because ALDH
neg and CD326
low fractions also generated ALDH
pos and CD326
hi cells, respectively. These data suggest that ALDH activity is probably a major candidate marker to enrich thyroid CSCs but not universal; other markers such as CD326 that regulate different CSC properties may exist.
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