Garre Elena, Gustafsson Anna, Leiva Maria Carmen, Håkansson Joakim, Ståhlberg Anders, Kovács Anikó, Landberg Göran
Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, Sahlgrenska Center for Cancer Research, University of Gothenburg, SE-41390 Gothenburg, Sweden.
Department of Clinical Pathology, Sahlgrenska University Hospital, SE-41345 Gothenburg, Sweden.
Cancers (Basel). 2022 Apr 26;14(9):2172. doi: 10.3390/cancers14092172.
Breast cancer is a heterogeneous disease in terms of cellular and structural composition, and besides acquired aggressive properties in the cancer cell population, the surrounding tumor microenvironment can affect disease progression and clinical behaviours. To specifically decode the clinical relevance of the cancer promoting effects of individual tumor microenvironments, we performed a comprehensive test of 110 breast cancer samples using a recently established -like 3D cell culture platform based on patient-derived scaffolds (PDSs). Cell-free PDSs were recellularized with three breast cancer cell lines and adaptation to the different patient-based microenvironments was monitored by quantitative PCR. Substantial variability in gene expression between individual PDS cultures from different patients was observed, as well as between different cell lines. Interestingly, specific gene expression changes in the PDS cultures were significantly linked to prognostic features and clinical information from the original cancer. This link was even more pronounced when ERα-status of cell lines and PDSs matched. The results support that PDSs cultures, including a cancer cell line of relevant origin, can monitor the activity of the tumor microenvironment and reveal unique information about the malignancy-inducing properties of the individual cancer niche and serve as a future complementary diagnostic tool for breast cancer.
乳腺癌在细胞和结构组成方面是一种异质性疾病,除了癌细胞群体中获得的侵袭性特性外,周围的肿瘤微环境也会影响疾病进展和临床行为。为了具体解读单个肿瘤微环境促癌作用的临床相关性,我们使用了一个最近建立的基于患者来源支架(PDS)的类似3D细胞培养平台,对110个乳腺癌样本进行了全面测试。将无细胞的PDS用三种乳腺癌细胞系重新构建细胞,并通过定量PCR监测对不同患者来源微环境的适应性。观察到来自不同患者的单个PDS培养物之间以及不同细胞系之间基因表达存在显著差异。有趣的是,PDS培养物中的特定基因表达变化与原始癌症的预后特征和临床信息显著相关。当细胞系和PDS的雌激素受体α(ERα)状态匹配时,这种联系更加明显。结果表明,包含相关来源癌细胞系的PDS培养物可以监测肿瘤微环境的活性,并揭示有关单个癌症微环境致恶性特性的独特信息,有望作为乳腺癌未来的辅助诊断工具。