Noninvasive identification of viable cell populations in docetaxel-treated breast tumors using ferritin-based magnetic resonance imaging.
Noninvasive identification of viable cell populations in docetaxel-treated breast tumors using ferritin-based magnetic resonance imaging.
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DOI：
10.1371/journal.pone.0052931
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Moon WK
中科院分区：
文献类型：
--
作者：
Choi Y;Kim HS;Cho KW;Lee KM;Yi YJ;Eun SJ;Kim HJ;Woo J;Choi SH;Whangbo TK;Choi C;Noh DY;Moon WK
癌症干细胞（CSC）是高度致瘤性的，并且负责肿瘤进展和化学抗性。用于肿瘤内CSC群体在体内可视化的非侵入性成像方法将对新的CSC靶向治疗剂的开发产生相当大的影响。在这项研究中，人乳腺癌干细胞（BCSC）转导双报告基因（人铁蛋白重链[FTH]和增强型绿色荧光蛋白[EGFP]）移植到NOD/SCID小鼠，允许非侵入性跟踪BCSC衍生的群体。没有观察到由于铁蛋白过表达而引起的BCSC性质的变化。磁共振成像（MRI）显示BCSCs和FTH-BCSCs在体外和体内的信号强度（R2* 值）显着不同。此外，与对照肿瘤相比，即使在肿瘤大小发生变化之前，在多西他赛治疗的FTH-BCSC肿瘤中也检测到具有高R2* 值的不同像素群。组织学分析显示，在经紫杉醇治疗的FTH-BCSC肿瘤中，MRI显示高R2* 值的区域含有EGFP+/FTH+活细胞群，其中CD 44 +/CD 24 −细胞百分比较高。这些研究结果表明，基于铁蛋白的MRI提供了高空间分辨率和组织对比度，可以用作一种可靠的方法来识别化疗后来自BCSC的活细胞群，并可以作为一种新的工具来监测CSC靶向治疗在体内的疗效。
Cancer stem cells (CSCs) are highly tumorigenic and are responsible for tumor progression and chemoresistance. Noninvasive imaging methods for the visualization of CSC populations within tumors in vivo will have a considerable impact on the development of new CSC-targeting therapeutics. In this study, human breast cancer stem cells (BCSCs) transduced with dual reporter genes (human ferritin heavy chain [FTH] and enhanced green fluorescence protein [EGFP]) were transplanted into NOD/SCID mice to allow noninvasive tracking of BCSC-derived populations. No changes in the properties of the BCSCs were observed due to ferritin overexpression. Magnetic resonance imaging (MRI) revealed significantly different signal intensities (R2* values) between BCSCs and FTH-BCSCs in vitro and in vivo. In addition, distinct populations of pixels with high R2* values were detected in docetaxel-treated FTH-BCSC tumors compared with control tumors, even before the tumor sizes changed. Histological analysis revealed that areas showing high R2* values in docetaxel-treated FTH-BCSC tumors by MRI contained EGFP+/FTH+ viable cell populations with high percentages of CD44+/CD24− cells. These findings suggest that ferritin-based MRI, which provides high spatial resolution and tissue contrast, can be used as a reliable method to identify viable cell populations derived from BCSCs after chemotherapy and may serve as a new tool to monitor the efficacy of CSC-targeting therapies in vivo.
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影响因子：
11.2
作者：
Medarova Z;Rashkovetsky L;Pantazopoulos P;Moore A
通讯作者：
Moore A
DOI：
10.1073/pnas.1006732107
发表时间：
2010-10-19
影响因子：
11.1
作者：
Liu, Huiping;Patel, Manishkumar R.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
3.3
作者：
Liu, Wei;Frank, Joseph A.
通讯作者：
Frank, Joseph A.
影响因子：
14
作者：
Lim, Eun-Kyung;Kim, Hyun-Ouk;Haam, Seungjoo
通讯作者：
Haam, Seungjoo
影响因子：
3.3
作者：
Artemov, D;Mori, N;Bhujwalla, ZM
通讯作者：
Bhujwalla, ZM