Side populations of gastrointestinal cancers are not enriched in stem cells
Side populations of gastrointestinal cancers are not enriched in stem cells
复制标题
DOI：
10.1002/path.2307
复制
发表时间：
2008-04-01
影响因子：
7.3
通讯作者：
Wright, N. A.
中科院分区：
文献类型：
--
作者：
Burkert, J.;Otto, W. R.;Wright, N. A.
侧群（SP）表型，定义为利血平可阻断的流出核酸染料Hoechst 33342的能力，已经声称在几种人类正常组织、癌症和细胞系中富集干细胞，因此可用于鉴定和分离癌症干细胞。我们证明了SP组分的存在下，在所有七个测试的胃肠道癌细胞系。选择四种细胞系（HT 29、HGT 101、Caco 2和HRA19a1.1）进行关于干细胞特征的详细表型和行为分析。细胞表面标志物分析显示，与非SP细胞相反，SP完全缺乏CD 34的表达。然而，当细胞培养时，这种差异消失，使两个群体CD 34阳性。其他假定的干细胞标志物（CD 133、CD 44、Hes-1、β-连环蛋白、Musashi-1、Oct-4和CD 117）的表达在培养前后在SP和非SP上是相同的。分选的SP和非SP细胞在体外具有相似的克隆形成性，在体内具有相似的致瘤性，并且在体外和体内显示出相似的多潜能分化潜能。此外，培养流式细胞术分选的SP和非SP细胞表明，群体是相互转化的，每一个产生另一个。ABCG 2和Mdr-1，两种膜转运蛋白，已被认为是负责药物流出能力的SP细胞，包括Hoechst 33342，是相同的非SP和SP细胞，表明可能有额外的因素负责Hoechst流出属性在胃肠道癌SP细胞。在这里，我们表明，SP和非SP部分，虽然表型不同的人口，不不同的干细胞样细胞的数量或行为。因此，我们得出结论，SP表型作为干细胞的通用标志物的概念不适用于胃肠道癌细胞。这些发现与许多其他组织中的观察结果形成鲜明对比，并对未来寻找肠癌干细胞标记物具有重要意义。版权所有（C）2007大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
The side population (SP) phenotype, defined as the reserpine-blockable ability to efflux the nucleic acid dye Hoechst 33342, has been claimed to be enriched for stem cells in several human normal tissues, cancers and cell lines, and thus may be useful for the identification and isolation of cancer stem cells. We demonstrated the presence of SP fractions in all of seven tested gastrointestinal cancer cell lines. Four cell lines were selected (HT29, HGT101, Caco2 and HRA19a1.1) for detailed phenotypic and behavioural analysis with respect to stem cell characteristics. Cell surface marker analysis showed that, contrary to non-SP cells, the SPs entirely lack the expression of CD34. This difference, however, disappeared when the cells were cultured, rendering both populations CD34-positive. Expression of other putative stem cell markers (CD133, CD44, Hes-1, beta-catenin, Musashi-1, Oct-4 and CD117) was identical on SP and non-SPs before and after culturing. Sorted SP and non-SP cells were similarly clonogenic in vitro, tumourigenic in vivo, and displayed similar multipotential differentiation potential in vitro and in vivo. Additionally, culturing cytometrically-sorted SP and non-SP cells showed that the populations are interconvertible, each giving rise to the other. Expression of ABCG2 and Mdr-1, two membrane transporter proteins that have been suggested to be responsible for the drug-effluxing capacities of SP cells, including Hoechst 33342, was identical in non-SP and SP cells, indicating that there may be additional factors responsible for the Hoechst effluxing property in gastrointestinal cancer SP cells. Here, we show that the SP and non-SP fractions, albeit phenotypically distinct populations, do not differ with respect to stem cell-like cell number or behaviour. We thus conclude that the concept of the SP phenotype as a universal marker for stem cells does not apply to gastrointestinal cancer cells. These findings stand in contrast to the observations made in many other tissues and harbour important implications for the future search for intestinal cancer stem cell markers. Copyright (C) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.