Characterization of side population in thyroid cancer cell lines: Cancer stem-like cells are enriched partly but not exclusively
Characterization of side population in thyroid cancer cell lines: Cancer stem-like cells are enriched partly but not exclusively
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DOI：
10.1210/en.2006-1553
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发表时间：
2007-04-01
期刊：
影响因子：
4.8
通讯作者：
Yamashita, Shunichi
中科院分区：
文献类型：
--
作者：
Mitsutake, Norisato;Iwao, Atsuhiko;Yamashita, Shunichi
越来越多的证据表明，癌症含有自己的干细胞样细胞，称为癌症干细胞（CSC）。一个小的细胞亚群，称为侧群（SP），已被确定使用流式细胞仪分析。SP细胞具有排除DNA结合染料Hoechst 33342的能力，并且在多种正常组织中高度富集干细胞。由于CSC被认为是耐药的，因此癌症中的SP细胞可能含有CSC。我们最初研究了SP细胞在几种人甲状腺癌细胞系中的存在。ARO（0.25%）、FRO（0.1%）、NPA（0.06%）和WRO（0.02%）细胞中发现了一小部分SP细胞，但TPC 1细胞中未发现。分选后，SP细胞在培养物中产生SP和非SP细胞。SP细胞的克隆形成能力明显高于非SP细胞。此外，SP的患病率是依赖于在文化中的细胞密度，表明SP细胞优先存活在较低的细胞密度。基因芯片实验显示SP细胞与非SP细胞的基因表达谱存在差异，与干细胞相关的多个基因表达上调。然而，非SP群体也包含在裸鼠中致瘤的细胞，并且非SP细胞产生少量SP细胞。这些结果表明，肿瘤干细胞样细胞部分但不完全富集在SP群体中。阐明关键的致瘤人群可能有助于建立甲状腺癌的新疗法。
There is increasing evidence that cancers contain their own stem-like cells called cancer stem cells ( CSCs). A small subset of cells, termed side population ( SP), has been identified using flow cytometric analysis. The SP cells have the ability to exclude the DNA binding dye, Hoechst33342, and are highly enriched for stem cells in many kinds of normal tissues. Because CSCs are thought to be drug resistant, SP cells in cancers might contain CSCs. We initially examined the presence of SP cells in several human thyroid cancer cell lines. A small percentage of SP cells were found in ARO ( 0.25%), FRO ( 0.1%), NPA ( 0.06%), and WRO ( 0.02%) cells but not TPC1 cells. After sorting, the SP cells generated both SP and non-SP cells in culture. The clonogenic ability of SP cells was significantly higher than that of non-SP cells. Moreover, the SP prevalence was dependent on cell density in culture, suggesting that SP cells preferentially survived at lower cell density. Microarray experiment revealed differential gene expression profile between SP and non-SP cells, and several genes related to stemness were up-regulated. However, non-SP population also contained cells that were tumorigenic in nude mice, and non-SP cells generated a small number of SP cells. These results suggest that cancer stem-like cells are partly, but not exclusively, enriched in SP population. Clarifying the key tumorigenic population might contribute to the establishment of a novel therapy for thyroid cancer.