Complex display of putative tumor stem cell markers in the NCI60 tumor cell line panel.

Complex display of putative tumor stem cell markers in the NCI60 tumor cell line panel.
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DOI:
10.1002/stem.324
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发表时间:
2010-04
期刊:
Stem cells (Dayton, Ohio)
影响因子:
--
通讯作者:
Niederhuber JE
Niederhuber JE
中科院分区:
其他
文献类型:
--
作者:
Stuelten CH;Mertins SD;Busch JI;Gowens M;Scudiero DA;Burkett MW;Hite KM;Alley M;Hollingshead M;Shoemaker RH;Niederhuber JE

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肿瘤干细胞或癌起始细胞(CICs)是可以再生肿瘤或转移的单个肿瘤细胞。CIC的鉴定和分离仍然具有挑战性,并且已经描述了各种假定的CIC标记物。我们假设NCI60细胞系含有CIC并表达假定的CIC标记物。通过六色荧光活化细胞分选分析,研究了NCI60细胞单独和联合表达CIC表面标记(CD15、CD24、CD44、CD133、CD166、CD326、PgP)和醛脱氢酶的活性。所有研究的标记物均在NCI60细胞系中表达。单个标记的表达水平在60个细胞系中差异很大,单个标记的表达、简单的组合或共表达模式都与细胞系的集落形成能力无关。相反,在多维分析中,标志物表达模式与肿瘤类型相关。虽然一些表达模式与肿瘤实体(如基底乳腺癌)相关,但其他表达模式发生在不同的肿瘤类型中,并且主要与个体乳腺、肺、肾和黑色素瘤细胞系中更多间充质表型的表达相关。我们的数据首次表明,肿瘤细胞系显示CIC标记在一个复杂的模式,与肿瘤类型有关。标记物显示的复杂性和肿瘤类型特异性为细胞分选和其他方法的应用带来了挑战,这些方法用于分离假定的肿瘤干细胞群,并表明治疗靶向策略需要考虑到这一点。
Tumor stem cells or cancer initiating cells (CICs) are single tumor cells that can regenerate a tumor or a metastasis. The identification and isolation of CICs remain challenging, and a variety of putative CIC markers have been described. We hypothesized that cell lines of the NCI60 panel contain CICs and express putative CIC markers. We investigated expression of putative CIC surface markers (CD15, CD24, CD44, CD133, CD166, CD326, PgP) and the activity of aldehyde dehydrogenase in the NCI60 panel singly and in combination by six-color fluorescence-activated cell sorting analysis. All investigated markers were expressed in cell lines of the NCI60 panel. Expression levels of individual markers varied widely across the 60 cell lines, and neither single marker expression nor simple combinations nor co-expression patterns correlated with the colony-formation capacity of cell lines. Rather, marker expression patterns correlated with tumor types in multidimensional analysis. Whereas some expression patterns correlated with tumor entities such as basal breast cancer, other expression patterns occurred across different tumor types and largely related to expression of a more mesenchymal phenotype in individual breast, lung, renal, and melanoma cell lines. Our data for the first time demonstrate that tumor cell lines display CIC markers in a complex pattern that relates to the tumor type. The complexity and tumor type specificity of marker display creates challenges for the application of cell sorting and other approaches to isolation of putative tumor stem cell populations and suggests that therapeutic targeting strategies will need to take this into account.
CD44+ CD24( - )前列腺细胞是早期的癌症祖/干细胞,为预后不良的患者提供了模型。
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