Engineering tumors with 3D scaffolds
Engineering tumors with 3D scaffolds
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DOI：
10.1038/nmeth1085
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发表时间：
2007-10-01
期刊：
影响因子：
48
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
--
作者：
Fischbach, Claudia;Chen, Ruth;Mooney, David J.
微环境条件控制肿瘤发生，而允许体外和体内肿瘤建模的仿生培养系统可能会极大地帮助研究癌细胞对这些条件的依赖性。我们使用聚合物支架中的癌细胞设计了三维 (3D) 人类肿瘤模型，重现了代表体内肿瘤的微环境特征。引人注目的是，在该系统内进行 3D 培养后，肿瘤细胞的血管生成特征发生了显着改变，并且与体内形成的肿瘤更加接近。该模型中的细胞对化疗的敏感性也较低，并产生具有增强恶性潜力的肿瘤。我们评估了这些发现与同一模型中其他肿瘤细胞系 3D 培养的广泛相关性，并与标准 3D Matrigel 培养和体内实验进行比较。这种新的仿生模型可能提供广泛适用的3D培养系统来研究微环境条件对体外和体内肿瘤恶性肿瘤的影响。
Microenvironmental conditions control tumorigenesis and biomimetic culture systems that allow for in vitro and in vivo tumor modeling may greatly aid studies of cancer cells' dependency on these conditions. We engineered three-dimensional ( 3D) human tumor models using carcinoma cells in polymeric scaffolds that recreated microenvironmental characteristics representative of tumors in vivo. Strikingly, the angiogenic characteristics of tumor cells were dramatically altered upon 3D culture within this system, and corresponded much more closely to tumors formed in vivo. Cells in this model were also less sensitive to chemotherapy and yielded tumors with enhanced malignant potential. We assessed the broad relevance of these findings with 3D culture of other tumor cell lines in this same model, comparison with standard 3D Matrigel culture and in vivo experiments. This new biomimetic model may provide a broadly applicable 3D culture system to study the effect of microenvironmental conditions on tumor malignancy in vitro and in vivo.