Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment.

中文翻译：

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患者衍生的支架发现了促进微环境特性的乳腺癌。

肿瘤细胞与微环境相互作用，该微环境特异性地支持和促进肿瘤的发展。肿瘤环境中的关键成分已与各种侵略性癌症特征相关联，并可进一步影响具有特定功能的癌细胞亚群（包括癌症干细胞和迁移细胞）的存在。为了建立模型并进一步了解特定微环境的影响，我们开发了一个实验平台，使用无细胞的患者源支架（PDS），这些支架来自于已渗入标准乳腺癌细胞系的原发性乳腺癌。该PDS培养系统在癌细胞群的分化，上皮-间质转化，干细胞和增殖中诱导了一系列精心策划的变化，其中通过功能测定证实了癌症干细胞池的增加。此外，全球基因表达谱表明，PDS培养物与异种移植物培养物相似。不含细胞的PDS的质谱分析根据其蛋白质成分确定了与临床特性（包括肿瘤等级）相关的亚组。最后，我们观察到在PDS上生长的癌细胞中上皮-间质转化相关基因的诱导与乳腺癌患者的临床疾病复发显着相关。因此，患者来源的支架模拟了类似体内的生长条件，并揭示了有关肿瘤微环境恶性诱导特性的独特信息。不含细胞的PDS的质谱分析根据其蛋白质成分确定了与临床特性（包括肿瘤等级）相关的亚组。最后，我们观察到在PDS上生长的癌细胞中上皮-间质转化相关基因的诱导与乳腺癌患者的临床疾病复发显着相关。因此，患者来源的支架模拟了类似体内的生长条件，并揭示了有关肿瘤微环境恶性诱导特性的独特信息。不含细胞的PDS的质谱分析根据其蛋白质成分确定了与临床特性（包括肿瘤等级）相关的亚组。最后，我们观察到在PDS上生长的癌细胞中上皮-间质转化相关基因的诱导与乳腺癌患者的临床疾病复发显着相关。因此，患者来源的支架模拟了类似体内的生长条件，并揭示了有关肿瘤微环境恶性诱导特性的独特信息。