3D breast cancer microtissue reveals the role of tumor microenvironment on the transport and efficacy of free-doxorubicin in vitro
3D breast cancer microtissue reveals the role of tumor microenvironment on the transport and efficacy of free-doxorubicin in vitro
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DOI：
10.1016/j.actbio.2018.05.055
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发表时间：
2018-07-15
影响因子：
9.7
通讯作者：
Netti, Paolo A.
中科院分区：
文献类型：
--
作者：
Brancato, Virginia;Gioiella, Filomena;Netti, Paolo A.
3D癌症模型的使用将对药物筛选和开发产生伦理和经济影响，以促进减少临床前研究中使用的动物。然而，为了有效，这样的癌症替代物必须保持体内模型的生理相关性，以便提供关于药物功效的现实信息。为了弄清楚3D癌症模型的结构和组成对其肿瘤模拟能力的作用，在这里，我们研究了多柔比星（DOX），一种众所周知的抗癌分子在两种不同的3D癌症模型中的疗效：我们的3D乳腺癌微组织（3D-mu TP）与以球体模型（sph）为代表的金标准。两种模型均采用癌相关成纤维细胞（CAF）和乳腺癌细胞（MCF-7）作为细胞成分获得。与球体模型不同，3D-mu TP被工程化以诱导CAF产生内源性细胞外基质。在用DOX处理后，将3D-mu TP与单培养物（单独的MCF-7）和共培养物（MCF-7/CAF）中的球状体进行比较，以研究细胞毒性效应、扩散转运和与癌症进展相关的蛋白质的表达。与球体模型相比，3D-mu TP显示出更高的DOX扩散系数和更低的细胞活力。此外，一些与细胞连接相关的肿瘤生物标志物在两种模型中的表达也不同。(C)2018 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The use of 3D cancer models will have both ethical and economic impact in drug screening and development, to promote the reduction of the animals employed in preclinical studies. Nevertheless, to be effective, such cancer surrogates must preserve the physiological relevance of the in vivo models in order to provide realistic information on drugs' efficacy. To figure out the role of the architecture and composition of 3D cancer models on their tumor-mimicking capability, here we studied the efficacy of doxorubicin (DOX), a well-known anticancer molecule in two different 3D cancer models: our 3D breast cancer micro tissue (3D-mu TP) versus the golden standard represented by spheroid model (sph). Both models were obtained by using cancer associated fibroblast (CAF) and breast cancer cells (MCF-7) as cellular component. Unlike spheroid model, 3D-mu TP was engineered in order to induce the production of endogenous extracellular matrix by CAF. 3D-mu TP have been compared to spheroid in mono- (MCF-7 alone) and co-culture (MCF-7/CAF), after the treatment with DOX in order to study cytotoxicity effect, diffusional transport and expression of proteins related to cancer progression. Compared to the spheroid model, 3D-mu TP showed higher diffusion coefficient of DOX and lower cell viability. Also, the expression of some tumoral biomarkers related to cell junctions were different in the two models. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.