Analysis of multiple markers for cancer stem-like cells in human thyroid carcinoma cell lines
Analysis of multiple markers for cancer stem-like cells in human thyroid carcinoma cell lines
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DOI：
10.1507/endocrj.ej13-0526
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发表时间：
2014-05-20
影响因子：
2
通讯作者：
Mitsutake, Norisato
中科院分区：
文献类型：
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作者：
Shimamura, Mika;Nagayama, Yuji;Mitsutake, Norisato
癌症干细胞（Cancer stem-样细胞，CSCs）在癌症的发生和发展中起着重要的作用。已经用几种标记物分离出了CSCs，但甲状腺CSCs的标记物仍有待证实。因此，我们对甲状腺CSC标志物进行了全面的搜索。采用8种甲状腺癌细胞系（FRO、KTC1/2/3、TPC1、WRO、ACT1和8505C），研究了9种细胞表面标志物（CD13、CD15、CD24、CD44、CD90、CD117、CD133、CD166和CD326）的表达和醛脱氢酶（ALDH）活性，以及它们在体外和体内形成球体的能力。其中，4个细胞系（FRO、KTC3、ACT1和8505C）同时具有这两种能力；然而，未观察到CSCs的常见标记物。形成球体的能力模式与肿瘤形成的能力模式完全匹配，表明我们的球体试验对评估肿瘤形成能力有价值。接下来，使用这些标记物对细胞进行分类，并进行球体试验。在三个细胞系（PRO、KTC3和ACT 1）中，ALDH（Pos）细胞比ALDH（阴性）细胞表现出更高的球体形成能力，而在其他细胞中则没有。CD326（hi）似乎也是仅在FRO细胞中的候选标记物。然而，这些亚群并没有遵循经典的分层模型，因为ALDH（阴性）和CD326（低）部分也分别产生ALDH（Pos）和CD326（hi）细胞。这些数据表明ALDH活性可能是甲状腺CSCs富集的主要候选标志物，但不是普遍的；可能存在其他标记物，如CD326，调节不同的CSC特性。
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 (PRO, KTC3, and ACT 1), 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.