A Facile, In Vitro 384-Well Plate System to Model Disseminated Tumor Cells in the Bone Marrow Microenvironment
A Facile, In Vitro 384-Well Plate System to Model Disseminated Tumor Cells in the Bone Marrow Microenvironment
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DOI：
10.1007/978-1-4939-7371-2_15
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发表时间：
2018-01-01
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影响因子：
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通讯作者：
Luker, Gary D.
中科院分区：
文献类型：
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作者：
Buschhaus, Johanna M.;Luker, Kathryn E.;Luker, Gary D.
骨髓播散性肿瘤细胞（DTC）是休眠的癌细胞，在患者缓解后在骨髓龛中潜伏多年，然后可能恢复到增殖状态，导致癌症复发。DTC存在于具有生理重要性的间充质干细胞的骨髓环境中，这些间充质干细胞通常受到化疗治疗的负面影响。目前，很少有DTC模型能够重现其休眠表型，同时产生足够的样本来准确量化癌症和周围基质细胞的行为。我们提出了一个三维球体为基础的模型系统，使用双色生物发光成像来量化不同的细胞活力，在响应各种化合物。我们成功地筛选了选择性消除癌细胞与支持性基质细胞的化合物，并与体内功效进行了比较。球状体共培养系统成功地模拟了DTC在骨髓微环境中的关键方面，促进了化合物选择性消除DTC的测试。
Bone marrow disseminated tumor cells (DTCs) are dormant cancer cells that harbor themselves in a bone marrow niche for years after patient remission before potentially returning to a proliferative state, causing recurrent cancer. DTCs reside in bone marrow environments with physiologically important mesenchymal stem cells that are often negatively affected by chemotherapy treatments. Currently, there are very few models of DTCs that recapitulate their dormant phenotype while producing enough samples to accurately quantify cancer and surrounding stromal cell behaviors. We present a three-dimensional spheroid-based model system that uses dual-color bioluminescence imaging to quantify differential cell viability in response to various compounds. We successfully screened for compounds that selectively eliminated cancer cells versus supportive stromal cells and verified results with comparison to efficacy in vivo. The spheroid coculture system successfully modeled key aspects of DTCs in the bone marrow microenvironment, facilitating testing for compounds to selectively eliminate DTCs.