The cancer microenvironment influences tumor progression and metastasis and is pivotal to consider when designing in vivo-like cancer models. Current preclinical testing platforms for cancer drug development are mainly limited to 2D cell culture systems that poorly mimic physiological environments and traditional, low throughput animal models. The aim of this work was to produce a tunable testing platform based on 3D printed scaffolds (3DPS) with a simple geometry that, by extracellular components and response of breast cancer reporter cells, mimics patient-derived scaffolds (PDS) of breast cancer. Here, the biocompatible polysaccharide alginate was used as base material to generate scaffolds consisting of a 3D grid containing periostin and hydroxyapatite. Breast cancer cell lines (MCF7 and MDA-MB-231) produced similar phenotypes and gene expression levels of cancer stem cell, epithelial–mesenchymal transition, differentiation and proliferation markers when cultured on 3DPS and PDS, contrasting conventional 2D cultures. Importantly, cells cultured on 3DPS and PDS showed scaffold-specific responses to cytotoxic drugs (doxorubicin and 5-fluorouracil) that were different from 2D cultured cells. In conclusion, the data presented support the use of a tunable alginate-based 3DPS as a tumor model in breast cancer drug discovery.

癌症微环境影响肿瘤进展和转移，是体内设计时需要考虑的关键- 像癌症模型。目前用于癌症药物开发的临床前测试平台主要局限于难以模拟生理环境的二维细胞培养系统和传统的低通量动物模型。这项工作的目的是生产一个基于 3D 打印支架 (3DPS) 的可调测试平台，该平台具有简单的几何形状，通过细胞外成分和乳腺癌报告细胞的反应，模拟乳腺癌患者衍生的支架 (PDS)。在这里，生物相容性多糖藻酸盐被用作基础材料，以生成由含有骨膜素和羟基磷灰石的 3D 网格组成的支架。乳腺癌细胞系（MCF7 和 MDA-MB-231）产生相似的癌症干细胞表型和基因表达水平、上皮-间质转化、在 3DPS 和 PDS 上培养时的分化和增殖标志物，与传统的 2D 培养物形成对比。重要的是，在 3DPS 和 PDS 上培养的细胞对不同于 2D 培养细胞的细胞毒性药物（阿霉素和 5-氟尿嘧啶）表现出支架特异性反应。总之，所提供的数据支持使用基于海藻酸盐的可调 3DPS 作为乳腺癌药物发现中的肿瘤模型。