Jaganathan Hamsa, Gage Jacob, Leonard Fransisca, Srinivasan Srimeenakshi, Souza Glauco R, Dave Bhuvanesh, Godin Biana
1] Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 USA [2].
1] n3D Biosiences Inc, Houston, TX, 77030 USA [2].
Sci Rep. 2014 Oct 1;4:6468. doi: 10.1038/srep06468.
In this study, we investigate a novel in vitro model to mimic heterogeneous breast tumors without the use of a scaffold while allowing for cell-cell and tumor-fibroblast interactions. Previous studies have shown that magnetic levitation system under conventional culturing conditions results in the formation of three-dimensional (3D) structures, closely resembling in vivo tissues (fat tissue, vasculature, etc.). Three-dimensional heterogeneous tumor models for breast cancer were designed to effectively model the influences of the tumor microenvironment on drug efficiency. Various breast cancer cells were co-cultured with fibroblasts and then magnetically levitated. Size and cell density of the resulting tumors were measured. The model was phenotypically compared to in vivo tumors and examined for the presence of ECM proteins. Lastly, the effects of tumor stroma in the 3D in vitro model on drug transport and efficiency were assessed. Our data suggest that the proposed 3D in vitro breast tumor is advantageous due to the ability to: (1) form large-sized (millimeter in diameter) breast tumor models within 24 h; (2) control tumor cell composition and density; (3) accurately mimic the in vivo tumor microenvironment; and (4) test drug efficiency in an in vitro model that is comparable to in vivo tumors.
在本研究中,我们探究了一种新型体外模型,该模型可在不使用支架的情况下模拟异质性乳腺肿瘤,同时允许细胞间以及肿瘤与成纤维细胞间的相互作用。先前的研究表明,在传统培养条件下,磁悬浮系统会导致三维(3D)结构的形成,与体内组织(脂肪组织、脉管系统等)极为相似。设计用于乳腺癌的三维异质性肿瘤模型,以有效模拟肿瘤微环境对药物疗效的影响。将各种乳腺癌细胞与成纤维细胞共培养,然后进行磁悬浮处理。测量所得肿瘤的大小和细胞密度。对该模型与体内肿瘤进行表型比较,并检测细胞外基质蛋白的存在情况。最后,评估三维体外模型中肿瘤基质对药物转运和疗效的影响。我们的数据表明,所提出的三维体外乳腺肿瘤模型具有以下优势:(1)能够在24小时内形成大尺寸(直径达毫米级)的乳腺肿瘤模型;(2)可控制肿瘤细胞组成和密度;(3)能准确模拟体内肿瘤微环境;(4)可在与体内肿瘤相当的体外模型中测试药物疗效。