Breast cancer patient‐derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments,Journal of Cellular Physiology

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Breast cancer patient‐derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-12-23 , DOI: 10.1002/jcp.30191
Maria Carmen Leiva ₁ , Elena Garre ₁ , Anna Gustafsson ₁ , Andreas Svanström ₁ , Yalda Bogestål ₂ , Joakim Håkansson _{1,

2} , Anders Ståhlberg _{1,

3,

4} , Göran Landberg ₁

Affiliation

Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three‐dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell‐free patient‐derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo‐like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front‐line chemotherapy drugs 5‐fluorouracil, doxorubicin and paclitaxel in comparison to traditional two‐dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5‐fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T‐47D and MDA‐MB‐231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo‐like microenvironments.

中文翻译：

乳腺癌患者来源的支架作为监测人类肿瘤微环境中化疗反应的工具

乳腺癌是一种异质性疾病，肿瘤微环境（包括细胞外成分）在肿瘤进展中发挥着至关重要的作用，可能调节治疗反应。已使用不同的方法来开发能够概括细胞外基质复杂性的三维模型。在这里，我们使用由乳腺癌样本产生的无细胞患者来源支架（PDS），这些样本用癌细胞系进行再细胞化，作为药物测试的类体内培养系统。我们发现，与传统的二维细胞培养物相比，PDS 培养的 MCF7 癌细胞增强了对一线化疗药物 5-氟尿嘧啶、阿霉素和紫杉醇的耐药性。根据所使用的药物和浓度，适应环境的癌细胞的基因表达以不同的方式进行调节。高剂量的阿霉素会降低癌症干细胞的特征，而5-氟尿嘧啶会增加干细胞的特性并降低增殖表型。通过使用重新填充其他乳腺癌细胞系 T-47D 和 MDA-MB-231 的 PDS，我们观察到一般药物反应和细胞系特异性药物反应。总之，PDS 可用于检查细胞外基质对癌症药物反应的影响，并可用于在类体内微环境中测试新型化合物。

更新日期：2020-12-23

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