文章：

C57BL/6J小鼠中肥胖反应性三阴性乳腺癌同基因原位移植模型的建立与表征

Development and Characterization of Syngeneic Orthotopic Transplant Models of Obesity-Responsive Triple-Negative Breast Cancer in C57BL/6J Mice

原文发布日期：9 August 2024

DOI: 10.3390/cancers16162803

类型: Article

开放获取: 是

英文摘要：

Obesity is an established risk and progression factor for triple-negative breast cancer (TNBC), but preclinical studies to delineate the mechanisms underlying the obesity-TNBC link as well as strategies to break that link are constrained by the lack of tumor models syngeneic to obesity-prone mouse strains. C3(1)/SV40 T-antigen (C3-TAg) transgenic mice on an FVB genetic background develop tumors with molecular and pathologic features that closely resemble human TNBC, but FVB mice are resistant to diet-induced obesity (DIO). Herein, we sought to develop transplantable C3-TAg cell lines syngeneic to C57BL/6 mice, an inbred mouse strain that is sensitive to DIO. We backcrossed FVB-Tg(C3-1-TAg)cJeg/JegJ to C57BL/6 mice for ten generations, and spontaneous tumors from those mice were excised and used to generate four clonal cell lines (B6TAg1.02, B6TAg2.03, B6TAg2.10, and B6TAg2.51). We characterized the growth of the four cell lines in both lean and DIO C57BL/6J female mice and performed transcriptomic profiling. Each cell line was readily tumorigenic and had transcriptional profiles that clustered as claudin-low, yet markedly differed from each other in their rate of tumor progression and transcriptomic signatures for key metabolic, immune, and oncogenic signaling pathways. DIO accelerated tumor growth of orthotopically transplanted B6TAg1.02, B6TAg2.03, and B6TAg2.51 cells. Thus, the B6TAg cell lines described herein offer promising and diverse new models to augment the study of DIO-associated TNBC.

摘要翻译： 

肥胖是三阴性乳腺癌（TNBC）已明确的风险与进展因素，但阐明肥胖与TNBC关联机制以及阻断该关联策略的临床前研究，因缺乏与肥胖易感小鼠品系同源的肿瘤模型而受到限制。FVB遗传背景的C3(1)/SV40 T抗原（C3-TAg）转基因小鼠所发生的肿瘤具有与人类TNBC高度相似的分子及病理特征，但FVB小鼠对饮食诱导肥胖（DIO）具有抵抗性。本研究旨在建立与C57BL/6小鼠（一种对DIO敏感的近交系小鼠）同源的、可移植的C3-TAg细胞系。我们将FVB-Tg(C3-1-TAg)cJeg/JegJ小鼠与C57BL/6小鼠回交十代，切除这些小鼠的自发性肿瘤并建立了四个克隆细胞系（B6TAg1.02、B6TAg2.03、B6TAg2.10和B6TAg2.51）。我们在瘦型及DIO状态的C57BL/6J雌性小鼠中表征了这四个细胞系的生长特性，并进行了转录组分析。所有细胞系均具有显著的致瘤性，其转录谱均聚类为claudin-low亚型，但在肿瘤进展速率以及关键代谢、免疫和致癌信号通路的转录组特征方面存在显著差异。DIO加速了原位移植的B6TAg1.02、B6TAg2.03和B6TAg2.51细胞的肿瘤生长。因此，本文所述的B6TAg细胞系为增强DIO相关TNBC研究提供了前景广阔且多样化的新型模型。

原文链接：

Development and Characterization of Syngeneic Orthotopic Transplant Models of Obesity-Responsive Triple-Negative Breast Cancer in C57BL/6J Mice