Genetics and Genomics Science Program, Michigan State University, East Lansing, MI, USA.
Department of Physiology, Michigan State University, 2194 BPS Building 567 Wilson Road, East Lansing, MI, 48824, USA.
J Mammary Gland Biol Neoplasia. 2023 Jun 3;28(1):12. doi: 10.1007/s10911-023-09540-2.
Breast cancer is well-known to be a highly heterogenous disease. This facet of cancer makes finding a research model that mirrors the disparate intrinsic features challenging. With advances in multi-omics technologies, establishing parallels between the various models and human tumors is increasingly intricate. Here we review the various model systems and their relation to primary breast tumors using available omics data platforms. Among the research models reviewed here, breast cancer cell lines have the least resemblance to human tumors since they have accumulated many mutations and copy number alterations during their long use. Moreover, individual proteomic and metabolomic profiles do not overlap with the molecular landscape of breast cancer. Interestingly, omics analysis revealed that the initial subtype classification of some breast cancer cell lines was inappropriate. In cell lines the major subtypes are all well represented and share some features with primary tumors. In contrast, patient-derived xenografts (PDX) and patient-derived organoids (PDO) are superior in mirroring human breast cancers at many levels, making them suitable models for drug screening and molecular analysis. While patient derived organoids are spread across luminal, basal- and normal-like subtypes, the PDX samples were initially largely basal but other subtypes have been increasingly described. Murine models offer heterogenous tumor landscapes, inter and intra-model heterogeneity, and give rise to tumors of different phenotypes and histology. Murine models have a reduced mutational burden compared to human breast cancer but share some transcriptomic resemblance, and representation of many breast cancer subtypes can be found among the variety subtypes. To date, while mammospheres and three- dimensional cultures lack comprehensive omics data, these are excellent models for the study of stem cells, cell fate decision and differentiation, and have also been used for drug screening. Therefore, this review explores the molecular landscapes and characterization of breast cancer research models by comparing recent published multi-omics data and analysis.
乳腺癌是一种众所周知的高度异质性疾病。癌症的这一方面使得寻找一个能够反映不同内在特征的研究模型具有挑战性。随着多组学技术的进步,在各种模型和人类肿瘤之间建立相似性变得越来越复杂。在这里,我们使用现有的组学数据平台,回顾了各种模型系统及其与原发性乳腺癌的关系。在本文综述的研究模型中,乳腺癌细胞系与人类肿瘤的相似度最低,因为它们在长期使用过程中积累了许多突变和拷贝数改变。此外,个别蛋白质组学和代谢组学图谱与乳腺癌的分子图谱不重叠。有趣的是,组学分析表明,一些乳腺癌细胞系的初始亚型分类是不恰当的。在细胞系中,主要亚型都有很好的代表性,并与原发性肿瘤有一些共同特征。相比之下,患者来源的异种移植(PDX)和患者来源的类器官(PDO)在许多层面上更能模拟人类乳腺癌,使它们成为药物筛选和分子分析的合适模型。虽然患者来源的类器官分布在腔型、基底型和正常样亚型中,但 PDX 样本最初主要是基底型,但也越来越多地描述了其他亚型。小鼠模型提供了异质的肿瘤景观、模型内和模型间的异质性,并产生了不同表型和组织学的肿瘤。与人类乳腺癌相比,小鼠模型的突变负担较低,但具有一些转录组相似性,并且可以在多种亚型中找到许多乳腺癌亚型的代表。迄今为止,尽管类球体和三维培养缺乏全面的组学数据,但这些是研究干细胞、细胞命运决定和分化的极好模型,也已用于药物筛选。因此,本综述通过比较最近发表的多组学数据和分析,探讨了乳腺癌研究模型的分子景观和特征。
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