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A 3D bioprinter platform for mechanistic analysis of tumoroids and chimeric mammary organoids

机译:3D生物打印机平台用于机械分析类肿瘤和嵌合乳腺类器官

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摘要

The normal mammary microenvironment can suppress tumorigenesis and redirect cancer cells to adopt a normal mammary epithelial cell fate in vivo. Understanding of this phenomenon offers great promise for novel treatment and detection strategies in cancer, but current model systems make mechanistic insights into the process difficult. We have recently described a low-cost bioprinting platform designed to be accessible for basic cell biology laboratories. Here we report the use of this system for the study of tumorigenesis and microenvironmental redirection of breast cancer cells. We show our bioprinter significantly increases tumoroid formation in 3D collagen gels and allows for precise generation of tumoroid arrays. We also demonstrate that we can mimic published in vivo findings by co-printing cancer cells along with normal mammary epithelial cells to generate chimeric organoids. These chimeric organoids contain cancer cells that take part in normal luminal formation. Furthermore, we show for the first time that cancer cells within chimeric structures have a significant increase in 5-hydroxymethylcytosine levels as compared to bioprinted tumoroids. These results demonstrate the capacity of our 3D bioprinting platform to study tumorigenesis and microenvironmental control of breast cancer and highlight a novel mechanistic insight into the process of microenvironmental control of cancer.
机译:正常的乳腺微环境可以抑制肿瘤的发生,并使癌细胞重新定向以适应体内正常的乳腺上皮细胞的命运。对这种现象的理解为癌症的新颖治疗和检测策略提供了广阔的前景,但是当前的模型系统使对该过程的机械洞察变得困难。我们最近描述了一种低成本的生物打印平台,旨在供基础细胞生物学实验室使用。在这里,我们报告该系统用于乳腺癌细胞的肿瘤发生和微环境重定向的研究。我们证明了我们的生物打印机显着增加了3D胶原蛋白凝胶中类瘤的形成,并允许精确生成类瘤阵列。我们还证明了我们可以通过共同打印癌细胞以及正常的乳腺上皮细胞来产生嵌合的类器官来模仿已发表的体内发现。这些嵌合类器官含有参与正常管腔形成的癌细胞。此外,我们首次显示与生物打印类瘤相比,嵌合结构内的癌细胞在5-羟甲基胞嘧啶水平上有显着增加。这些结果证明了我们的3D生物打印平台研究乳腺癌的肿瘤发生和微环境控制的能力,并突出了对癌症微环境控制过程的新颖机制性见解。

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