2014 Volume 61 Issue 5 Pages 481-490
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), ALDHpos cells showed higher sphere forming ability than ALDHneg cells but not in other cells. CD326hi also appeared to be a candidate marker only in FRO cells. However, these subpopulations did not follow a classical hierarchical model because ALDHneg and CD326low fractions also generated ALDHpos and CD326hi 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.