Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1.
Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1.
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DOI：
10.1021/acscentsci.8b00313
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发表时间：
2018-08-22
影响因子：
18.2
通讯作者：
Chan J
中科院分区：
文献类型：
--
作者：
Anorma C;Hedhli J;Bearrood TE;Pino NW;Gardner SH;Inaba H;Zhang P;Li Y;Feng D;Dibrell SE;Kilian KA;Dobrucki LW;Fan TM;Chan J
癌症干细胞（CSC）是在复发期间促成治疗抗性表型的祖细胞。CSC存在于细胞培养物和更复杂的模型无法模拟的特定组织微环境中。因此，开发可以检测CSC并报告特定特性（例如，干细胞可塑性）对研究CSC生物学具有深远意义。在此，我们提出了AlDeSense，醛脱氢酶1A 1（ALDH 1A 1）和Ctrl-AlDeSense，一个匹配的非响应性试剂的开启荧光探针。虽然ALDH 1A 1有助于活性醛的解毒，但它也与干性相关，并且在CSC中高度升高。当用ALDH 1A 1处理时，AlDeSense表现出20倍的荧光增强。此外，我们建立了AlDeSense对一组常见的ALDH亚型具有选择性，并对一系列生物学相关物种表现出精致的化学稳定性。通过应用表面标记抗体染色、肿瘤球测定和致瘤性评估，我们证明表现出高AlDeSense信号强度的细胞具有CSC的特性。串联使用这些探针，我们已经通过流式细胞术和共聚焦成像在细胞水平上鉴定了CSC，并在动物模型中监测了它们的状态。癌症干细胞（CSC）在多种癌症中促成侵袭性或治疗抗性表型。由于ALDH 1A 1活性上调，AlDeSense AM在CSC中选择性开启。
Cancer stem cells (CSCs) are progenitor cells that contribute to treatment-resistant phenotypes during relapse. CSCs exist in specific tissue microenvironments that cell cultures and more complex models cannot mimic. Therefore, the development of new approaches that can detect CSCs and report on specific properties (e.g., stem cell plasticity) in their native environment have profound implications for studying CSC biology. Herein, we present AlDeSense, a turn-on fluorescent probe for aldehyde dehydrogenase 1A1 (ALDH1A1) and Ctrl-AlDeSense, a matching nonresponsive reagent. Although ALDH1A1 contributes to the detoxification of reactive aldehydes, it is also associated with stemness and is highly elevated in CSCs. AlDeSense exhibits a 20-fold fluorescent enhancement when treated with ALDH1A1. Moreover, we established that AlDeSense is selective against a panel of common ALDH isoforms and exhibits exquisite chemostability against a collection of biologically relevant species. Through the application of surface marker antibody staining, tumorsphere assays, and assessment of tumorigenicity, we demonstrate that cells exhibiting high AlDeSense signal intensity have properties of CSCs. Using these probes in tandem, we have identified CSCs at the cellular level via flow cytometry and confocal imaging, as well as monitored their states in animal models. Cancer stem cells (CSCs) contribute to aggressive or treatment-resistant phenotypes in a wide variety of cancers. AlDeSense AM selectively turns on in CSCs due to upregulated ALDH1A1 activity.
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影响因子：
5.1
作者：
Morgan, Cynthia A.;Hurley, Thomas D.
通讯作者：
Hurley, Thomas D.
影响因子：
5.1
作者：
Morgan, Cynthia A.;Parajuli, Bibek;Buchman, Cameron D.;Dria, Karl;Hurley, Thomas D.
通讯作者：
Hurley, Thomas D.
影响因子：
--
作者：
Lee CH;Yu CC;Wang BY;Chang WW
通讯作者：
Chang WW
影响因子：
5.1
作者：
Moreb, Jan S.;Ucar, Deniz;Han, Shuhong;Amory, John K.;Goldstein, Alex S.;Ostmark, Blanca;Chang, Lung-Ji
通讯作者：
Chang, Lung-Ji
影响因子：
41.2
作者：
Lee, Junmin;Abdeen, Amr A.;Kilian, Kristopher A.
通讯作者：
Kilian, Kristopher A.