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首页> 外文期刊>Journal of Cell Communication and Signaling >A reproducible scaffold-free 3D organoid model to study neoplastic progression in breast cancer
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A reproducible scaffold-free 3D organoid model to study neoplastic progression in breast cancer

机译：一种可重复的支架无组织器模型，用于研究乳腺癌的肿瘤进展

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While 3D cellular models are useful to study biological processes, gel-embedded organoids have large variability. This paper describes high-yield production of large (1mm diameter), scaffold-free, highly-spherical organoids in a one drop-one organoid format using MCF10A cells, a non-tumorigenic breast cell line. These organoids display a hollow lumen and secondary acini, and express mammary gland-specific and progenitor markers, resembling normal human breast acini. When subjected to treatment with TGF-, the hypoxia-mimetic reagent CoCl2, or co-culture with mesenchymal stem/stromal cells (MSC), the organoids increase collagen I production and undergo large phenotypic and morphological changes of neoplastic progression, which were reproducible and quantifiable. Advantages of this scaffold-free, 3D breast organoid model include high consistency and reproducibility, ability to measure cellular collagen I production without noise from exogenous collagen, and capacity to subject the organoid to various stimuli from the microenvironment and exogenous treatments with precise timing without concern of matrix binding. Using this system, we generated organoids fromprimary metaplastic mammarycarcinomas of MMTV-Cre;Ccn6(fl/fl) mice, which retained the high grade spindle cell morphology of the primary tumors.The platform is envisioned to be useful as a standardized 3D cellular model to study how microenvironmental factors influence breast tumorigenesis, and to potential therapeutics.
机译：虽然3D细胞模型对于研究生物方法有用，但凝胶嵌入的有机体具有大的变化。本文描述了使用MCF10A细胞，非致瘤乳腺细胞系的一滴有机体形式的大（直径），无支腿的无球形有机体的高屈服度产生的高屈服度的高度球形有机体。这些有机体显示中空腔和次级aciini，表达乳腺特异性和祖先标记，类似于正常的人类乳房acini。当用TGF的治疗方法，缺氧模拟试剂COCl2或与间充质茎/基质细胞（MSC）的共培养物时，有机体增加胶原蛋白I产生并经历肿瘤进展的大表型和形态变化，可重复和量化。这种无支腿的优点，3D乳房有机体模型包括高一致性和再现性，测量手机胶原蛋白的能力，没有来自外源胶原的噪音，以及将有机体对微环境和外源性处理进行各种刺激的能力，并不令人担忧。基质结合。使用该系统，我们生成有机体从MMTV-CRE的微生物间乳房术治疗MMTV-CRE; CCN6（FL / FL）小鼠，其保留了原发性肿瘤的高级主轴细胞形态。平台被认为是标准化的3D蜂窝模型研究微环境因素如何影响乳腺癌，以及潜在的治疗方法。

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