Mammosphere culture of metastatic breast cancer cells enriches for tumorigenic breast cancer cells.
Mammosphere culture of metastatic breast cancer cells enriches for tumorigenic breast cancer cells.
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DOI：
10.1186/bcr2106
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Burchell JM
中科院分区：
文献类型：
--
作者：
Grimshaw MJ;Cooper L;Papazisis K;Coleman JA;Bohnenkamp HR;Chiapero-Stanke L;Taylor-Papadimitriou J;Burchell JM
潜在的乳腺癌干细胞的鉴定是重要的，因为干细胞的特性表明它们对常规形式的治疗具有抗性。已经提出了几种分离或富集致瘤性乳腺癌干细胞的技术，包括（a）在非粘附非分化条件下培养细胞以形成乳腺球和（B）通过细胞的表面表型（表达CD 24和CD 44）分选细胞。我们在无血清的非粘附条件下培养了乳腺癌患者胸腔积液中发现的转移性细胞，以形成乳腺球。从这些乳腺球中分离的细胞用于确定这些培养物的致瘤性。记录了来自胸腔积液的未培养细胞和乳腺球上的CD 24和CD 44表达。我们发现，大多数（20/27）胸腔积液检测含有细胞能够形成不同大小的乳腺球，可以传代。在解离和用血清接种到贴壁培养皿上后，细胞可以分化，如通过细胞角蛋白和MUC 1的表达增加所确定的。对来自21个样品的未培养细胞上的CD 24和CD 44的表面表达的分析显示，来自一些样品的细胞分离成两个群体，但一些没有。可被认为是CD 44 +/CD 24低/-的细胞的比例是高度可变的，并且似乎与形成较大乳腺球的能力无关。在严重联合免疫缺陷病（SCID）小鼠中测试的8个胸腔积液乳腺球中，发现4个在注射5，000个或更少细胞时诱导肿瘤，而相同数量的未培养细胞不会形成肿瘤。诱发肿瘤的能力似乎与产生更大的乳腺球的能力相关。来自高度致瘤性样品（PE 14）的未培养细胞对于CD 24和CD 44的表面表达均为阴性。本文首次表明，胸腔积液的乳腺球培养物富集了能够在SCID小鼠中诱导肿瘤的细胞。这些数据表明，这些转移性细胞的mammosphere培养可以提供一个非常合适的模型，用于研究致瘤“干”细胞对治疗药物的敏感性，并进一步表征乳腺癌细胞的肿瘤诱导亚群。
The identification of potential breast cancer stem cells is of importance as the characteristics of stem cells suggest that they are resistant to conventional forms of therapy. Several techniques have been proposed to isolate or enrich for tumorigenic breast cancer stem cells, including (a) culture of cells in non-adherent non-differentiating conditions to form mammospheres and (b) sorting of the cells by their surface phenotype (expression of CD24 and CD44). We have cultured metastatic cells found in pleural effusions from breast cancer patients in non-adherent conditions without serum to form mammospheres. Dissociated cells from these mammospheres were used to determine the tumorigenicity of these cultures. Expression of CD24 and CD44 on uncultured cells and mammospheres derived from the pleural effusions was documented. We found that the majority (20/27) of the pleural effusions tested contained cells capable of forming mammospheres of varying sizes that could be passaged. After dissociation and plating with serum onto adherent dishes, the cells can differentiate, as determined by the increased expression of cytokeratins and MUC1. Analysis of surface expression of CD24 and CD44 on uncultured cells from 21 of the samples showed that the cells from some samples separated into two populations, but some did not. The proportion of cells that could be considered CD44+/CD24low/- was highly variable and did not appear to correlate with the ability to form the larger mammospheres. Of eight pleural effusion mammospheres tested in severe combined immunodeficiency disease (SCID) mice, four were found to induce tumours when only 5,000 or fewer cells were injected, whereas the same number of uncultured cells did not form tumours. The ability to induce tumours appeared to correlate with the ability to produce the larger mammospheres. Uncultured cells from a highly tumorigenic sample (PE14) were uniformly negative for surface expression of both CD24 and CD44. This paper shows, for the first time, that mammosphere culture of pleural effusions enriches for cells capable of inducing tumours in SCID mice. The data suggest that mammosphere culture of these metastatic cells could provide a highly appropriate model for studying the sensitivity of the tumorigenic 'stem' cells to therapeutic agents and for further characterisation of the tumour-inducing subpopulation of breast cancer cells.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
8.5
作者：
Petersen, OW;Gudjonsson, T;Villadsen, R
通讯作者：
Villadsen, R
影响因子：
6.4
作者：
Cariati, Massimiliano;Naderi, Ali;Purushotham, Anand D.
通讯作者：
Purushotham, Anand D.
DOI：
10.1073/pnas.0606599104
发表时间：
2007-01-09
影响因子：
11.1
作者：
Woodward, Wendy A.;Chen, Mercy S.;Rosen, Jeffrey M.
通讯作者：
Rosen, Jeffrey M.
DOI：
10.1007/bf01005976
发表时间：
1990-10-01
期刊：
HISTOCHEMICAL JOURNAL
影响因子：
--
作者：
BARTEK, J;BARTKOVA, J;TAYLORPAPADIMITRIOU, J
通讯作者：
TAYLORPAPADIMITRIOU, J