Profiling of normal and malignant breast tissue show CD44high/CD24low phenotype as a predominant stem/progenitor marker when used in combination with Ep-CAM/CD49f markers.
Profiling of normal and malignant breast tissue show CD44high/CD24low phenotype as a predominant stem/progenitor marker when used in combination with Ep-CAM/CD49f markers.
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DOI：
10.1186/1471-2407-13-289
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发表时间：
2013-06-14
期刊：
影响因子：
3.8
通讯作者：
Adra CN
中科院分区：
文献类型：
--
作者：
Ghebeh H;Sleiman GM;Manogaran PS;Al-Mazrou A;Barhoush E;Al-Mohanna FH;Tulbah A;Al-Faqeeh K;Adra CN
越来越多的证据表明，癌症是从一小群被称为癌症干细胞（CSC）的干细胞样细胞开始和发展起来的。CSC及其在正常乳腺中的对应物的确切表型尚不清楚。在这项研究中，我们的目的是评估正常乳腺上皮细胞群和恶性上皮细胞群中干细胞/祖细胞的表型和功能。使用13种广泛使用的干细胞/祖细胞标记物单独或联合进行多参数（多达9种颜色）细胞分选，对从正常和恶性乳腺中分离的新鲜细胞进行分选。通过在体外形成菌落和乳房微球的能力对分类后的种群进行功能评估。我们第一次比较了正常乳房和恶性乳房的干细胞/祖细胞标记。在所有测试的标记中，我们发现cd44高/ cd24低细胞表面标记组合在选择正常上皮祖细胞方面是最有效的。进一步分离CD44high/CD24low阳性细胞表明，该表型在Ep-CAM-/ CD49f +细胞中选择腔内祖细胞，在Ep-CAM-/low/CD49f +细胞中富集基底祖细胞。另一方面，原发性乳腺癌样本以腔内Ep-CAMhigh为主，在CD49fneg和CD49f +癌细胞组中均存在CD44high/CD24low细胞。然而，在功能上，CSC以CD49f +为主，建议使用CD44high/CD24low与Ep-CAM/CD49f细胞表面标记物联合进一步富集CSC。我们的研究清楚地表明，当与Ep-CAM/CD49f参比标记物联合使用时，CD44high/CD24low表型的正常和恶性乳腺细胞都具有最高的干细胞/祖细胞能力。我们相信这项广泛的表征研究将有助于了解乳腺癌的癌变、异质性和耐药性。
Accumulating evidence supports cancer to initiate and develop from a small population of stem-like cells termed as cancer stem cells (CSC). The exact phenotype of CSC and their counterparts in normal mammary gland is not well characterized. In this study our aim was to evaluate the phenotype and function of stem/progenitor cells in normal mammary epithelial cell populations and their malignant counterparts. Freshly isolated cells from both normal and malignant human breasts were sorted using 13 widely used stem/progenitor cell markers individually or in combination by multi-parametric (up to 9 colors) cell sorting. The sorted populations were functionally evaluated by their ability to form colonies and mammospheres, in vitro. We have compared, for the first time, the stem/progenitor markers of normal and malignant breasts side-by-side. Amongst all markers tested, we found CD44high/CD24low cell surface marker combination to be the most efficient at selecting normal epithelial progenitors. Further fractionation of CD44high/CD24low positive cells showed that this phenotype selects for luminal progenitors within Ep-CAMhigh/CD49f + cells, and enriches for basal progenitors within Ep-CAM-/low/CD49f + cells. On the other hand, primary breast cancer samples, which were mainly luminal Ep-CAMhigh, had CD44high/CD24low cells among both CD49fneg and CD49f + cancer cell fractions. However, functionally, CSC were predominantly CD49f + proposing the use of CD44high/CD24low in combination with Ep-CAM/CD49f cell surface markers to further enrich for CSC. Our study clearly demonstrates that both normal and malignant breast cells with the CD44high/CD24low phenotype have the highest stem/progenitor cell ability when used in combination with Ep-CAM/CD49f reference markers. We believe that this extensive characterization study will help in understanding breast cancer carcinogenesis, heterogeneity and drug resistance.
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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：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
DOI：
10.1186/bcr1673
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fillmore C;Kuperwasser C
通讯作者：
Kuperwasser C
影响因子：
11.2
作者：
Frank, NY;Margaryan, A;Frank, MH
通讯作者：
Frank, MH
影响因子：
6.4
作者：
Cariati, Massimiliano;Naderi, Ali;Purushotham, Anand D.
通讯作者：
Purushotham, Anand D.