Screening Estrogen Receptor Modulators in a Paper-Based Breast Cancer Model.
Screening Estrogen Receptor Modulators in a Paper-Based Breast Cancer Model.
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DOI：
10.1021/acs.analchem.8b02486
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发表时间：
2018-10-16
影响因子：
7.4
通讯作者：
Lockett MR
中科院分区：
文献类型：
--
作者：
Whitman NA;Lin ZW;DiProspero TJ;McIntosh JC;Lockett MR
与急性和长期暴露于雌激素受体（ER）调节剂相关的健康风险导致了共同努力，以确定和优先考虑环境中存在的潜在干扰物。ER激动剂和拮抗剂用终点测定法鉴定，定量暴露后雌激素受体α表达（ER+）细胞单层中细胞增殖或基因反式激活的变化。虽然这些单层培养物可以以高度平行化的方式制备、给药和分析，但它们不能准确预测ER调节剂在体内的效力。需要更好地预测组织或器官水平反应的生理相关模型系统。为了解决这一需求，我们在这里描述了一个筛选平台，能够定量评估ER调节剂在96个化学分离的三维文化。这些培养物在蜡图案纸支架中得到支持，其设计与先前描述的纸基设置相比提高了性能和通量。为了突出纸基培养物用于毒性筛选的潜力，我们用基于内切酶的报告基因测定法测量了已知ER调节剂的效力。我们还定量了雌二醇存在下两种ER+细胞系的增殖和侵袭。尽管目前的设置无法更好地预测ER调节剂的体内效力比单层培养，结果表明，该平台的潜力，以支持越来越复杂的和生理相关的组织样结构的环境化学风险评估。
The health risks associated with acute and prolonged exposure to estrogen receptor (ER) modulators has led to a concerted effort to identify and prioritize potential disruptors present in the environment. ER agonists and antagonists are identified with end-point assays, quantifying changes in cellular proliferation or gene transactivation in monolayers of estrogen receptor alpha expressing (ER+) cells upon exposure. While these monolayer cultures can be prepared, dosed, and analyzed in a highly parallelized manner, they are unable to predict the potencies of ER modulators in vivo accurately. Physiologically relevant model systems that better predict tissue- or organ-level responses are needed. To address this need, we describe here a screening platform capable of quantitatively assessing ER modulators in 96 chemically isolated 3D cultures. These cultures are supported in wax-patterned paper scaffolds whose design has improved performance and throughput over previously described paper-based setups. To highlight the potential of paper-based cultures for toxicity screens, we measured the potency of known ER modulators with a luciferase-based reporter assay. We also quantified the proliferation and invasion of two ER+ cell lines in the presence of estradiol. Despite the inability of the current setup to better predict in vivo potencies of ER modulators than monolayer cultures, the results demonstrate the potential of this platform to support increasingly complex and physiologically relevant tissue-like structures for environmental chemical risk assessment.
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影响因子：
3.7
作者：
Barcus CE;Holt EC;Keely PJ;Eliceiri KW;Schuler LA
通讯作者：
Schuler LA
影响因子：
7.7
作者：
Cho S;Yoon JY
通讯作者：
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影响因子：
6.9
作者：
Bouris, Panagiotis;Skandalis, Spyros S.;Karamanos, Nikos K.
通讯作者：
Karamanos, Nikos K.
影响因子：
3.2
作者：
Akahori, Yumi;Nakai, Makoto;Ohtaki, Masahiro
通讯作者：
Ohtaki, Masahiro
用于细胞培养、药物筛选和质谱传感的工程细胞兼容纸芯片
影响因子：
10
作者：
Chen, Qiushui;He, Ziyi;Lin, Jin-Ming
通讯作者：
Lin, Jin-Ming