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首页> 外文期刊>Journal of cellular physiology. >Breast cancer patient-derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments
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Breast cancer patient-derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments

机译:乳腺癌patient-derived支架作为一种工具监测人类肿瘤化疗反应微环境

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摘要

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 pheno-type. 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.
机译:乳腺癌是一种异质性疾病的地方肿瘤微环境,包括细胞外组件,在肿瘤中扮演着关键角色发展,潜在的调节治疗响应。三维模型能够发展摘要细胞外的复杂性矩阵。支架(pds)生成的乳腺癌样品是recellularized与癌症细胞行作为药物在vivo-like文化系统测试。细胞增加了抵抗一线化疗药物5 -氟尿嘧啶,阿霉素、紫杉醇相比传统的二维细胞培养。对环境适应的基因表达癌症细胞在不同的调制方式根据所使用的药物和浓度。高剂量的阿霉素降低癌症干细胞细胞的特性,而5 -氟尿嘧啶增加具备干细胞增殖和减少pheno-type。乳腺癌细胞系,T-47D和mda - mb - 231,我们观察到一般和特定细胞系药物反应。检查细胞外基质的影响抗癌药物反应和用于测试的小说化合物在vivo-like微环境。

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