Modeling Ewing sarcoma tumors in vitro with 3D scaffolds
Modeling Ewing sarcoma tumors in vitro with 3D scaffolds
复制标题
DOI：
10.1073/pnas.1221403110
复制
发表时间：
2013-04-16
影响因子：
11.1
通讯作者：
Ludwig, Joseph A.
中科院分区：
文献类型：
--
作者：
Fong, Eliza Li Shan;Lamhamedi-Cherradi, Salah-Eddine;Ludwig, Joseph A.
肿瘤微环境对癌症进展和转移的显著生物学影响在过去十年中得到了越来越多的认可，但大多数临床前药物测试仍然依赖于传统的2D细胞培养系统。尽管单层培养物概括了临床观察到的一些表型特征，但它们在模拟全范围微环境线索（例如由3D细胞-细胞和细胞-细胞外基质相互作用引起的微环境线索）方面的能力有限。为了解决这些缺点，我们建立了一个离体3D尤文肉瘤模型，该模型密切模仿人类肿瘤的形态学，生长动力学和蛋白质表达谱。我们观察到，尤文肉瘤细胞培养在多孔三维电纺聚（ε-己内酯）支架不仅是更耐传统的细胞毒性药物比细胞在2D单层培养，但也表现出显着差异的表达模式的胰岛素样生长因子-1受体/哺乳动物靶雷帕霉素途径。这种骨微环境的3D模型可能对骨肉瘤的机制研究具有广泛的适用性，并显示出增强这些恶性肿瘤候选药物的临床前评价的潜力。
The pronounced biological influence of the tumor microenvironment on cancer progression and metastasis has gained increased recognition over the past decade, yet most preclinical antineoplastic drug testing is still reliant on conventional 2D cell culture systems. Although monolayer cultures recapitulate some of the phenotypic traits observed clinically, they are limited in their ability to model the full range of microenvironmental cues, such as ones elicited by 3D cell-cell and cell-extracellular matrix interactions. To address these shortcomings, we established an ex vivo 3D Ewing sarcoma model that closely mimics the morphology, growth kinetics, and protein expression profile of human tumors. We observed that Ewing sarcoma cells cultured in porous 3D electrospun poly(epsilon-caprolactone) scaffolds not only were more resistant to traditional cytotoxic drugs than were cells in 2D monolayer culture but also exhibited remarkable differences in the expression pattern of the insulin-like growth factor-1 receptor/mammalian target of rapamycin pathway. This 3D model of the bone microenvironment may have broad applicability for mechanistic studies of bone sarcomas and exhibits the potential to augment preclinical evaluation of antineoplastic drug candidates for these malignancies.