Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts.
Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts.
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DOI：
10.1038/srep18821
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发表时间：
2016-01-06
影响因子：
4.6
通讯作者：
Nolte D
中科院分区：
文献类型：
--
作者：
Merrill D;An R;Sun H;Yakubov B;Matei D;Turek J;Nolte D
三维（3D）组织培养正在取代传统的二维（2D）培养，用于癌症药物开发。然而，由于缺乏能够从活体组织深处提取高含量信息的灵敏光学探针，尚未报道将体外3D模型与来源于相同细胞系的体内模型进行直接比较。在这里，我们报告使用生物动力成像（BDI）来测量三维活组织对铂的反应。BDI结合了低相干数字全息和细胞内多普勒光谱来研究肿瘤药物反应。人卵巢癌细胞系在体外培养成三维多细胞单培养球体或在裸鼠体内异种移植。裸鼠体内培养的对铂敏感的人卵巢细胞系的异种移植物片段在体外暴露于铂时显示出快速和显著的诱导细胞死亡特征，而在体外培养的相应的3D多细胞球体则显示出可以忽略不计的反应。体内和体外生长之间的药物反应差异对于通过患者或患者来源的异种移植物的肿瘤活检来预测化疗反应具有重要意义。
Three-dimensional (3D) tissue cultures are replacing conventional two-dimensional (2D) cultures for applications in cancer drug development. However, direct comparisons of in vitro 3D models relative to in vivo models derived from the same cell lines have not been reported because of the lack of sensitive optical probes that can extract high-content information from deep inside living tissue. Here we report the use of biodynamic imaging (BDI) to measure response to platinum in 3D living tissue. BDI combines low-coherence digital holography with intracellular Doppler spectroscopy to study tumor drug response. Human ovarian cancer cell lines were grown either in vitro as 3D multicellular monoculture spheroids or as xenografts in nude mice. Fragments of xenografts grown in vivo in nude mice from a platinum-sensitive human ovarian cell line showed rapid and dramatic signatures of induced cell death when exposed to platinum ex vivo, while the corresponding 3D multicellular spheroids grown in vitro showed negligible response. The differences in drug response between in vivo and in vitro growth have important implications for predicting chemotherapeutic response using tumor biopsies from patients or patient-derived xenografts.