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雌激素受体阳性乳腺癌转移休眠的临床前小鼠管内模型(MIND)研究。

Preclinical Mouse Intraductal Model (MIND) to Study Metastatic Dormancy in Estrogen Receptor-Positive Breast Cancer.

机构信息

ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland.

Division of Breast Cancer Research, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.

出版信息

Methods Mol Biol. 2024;2811:101-112. doi: 10.1007/978-1-0716-3882-8_7.

DOI:10.1007/978-1-0716-3882-8_7
PMID:39037652
Abstract

Here, we describe a clinically relevant xenograft model of hormone receptor-positive breast cancer that maintains estrogen receptor (ER) status without the need for exogenous supplementation of hormones. The naturally low 17-β-estradiol levels in host mice recapitulate levels seen in post-menopausal women. By introducing breast cancer cells directly into their "natural" microenvironment of the milk ducts, these cells maintain hormone receptor status, model the clinical progression of the disease, and develop ER metastatic lesions or dormant micrometastatic lesions in the case of ER BC. With the use of GFP/RFP:Luc2 reporters, we can monitor in vivo tumour growth and conduct ex vivo metastases assays to evaluate dormant metastatic cell harboring organs. Upon recovery of metastatic cells from ER breast cancer models, downstream analyses can be conducted to assess the relationship between epithelial plasticity and metastatic dormancy.

摘要

在这里,我们描述了一种具有临床相关性的激素受体阳性乳腺癌异种移植模型,该模型无需外源性激素补充就能维持雌激素受体(ER)状态。宿主小鼠中天然低水平的 17-β-雌二醇水平再现了绝经后妇女的水平。通过将乳腺癌细胞直接引入其乳腺导管的“天然”微环境中,这些细胞维持激素受体状态,模拟疾病的临床进展,并在 ERBC 的情况下发展 ER 转移病灶或休眠微转移病灶。通过使用 GFP/RFP:Luc2 报告基因,我们可以监测体内肿瘤生长并进行离体转移实验,以评估携带休眠转移细胞的器官。从 ER 乳腺癌模型中回收转移细胞后,可以进行下游分析,以评估上皮可塑性与转移休眠之间的关系。

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本文引用的文献

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Current and future burden of breast cancer: Global statistics for 2020 and 2040.乳腺癌的现状和未来负担:2020 年和 2040 年全球统计数据。
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Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence.上皮-间充质可塑性决定了雌激素受体阳性乳腺癌的休眠和上皮转化驱动复发。
Nat Commun. 2022 Aug 25;13(1):4975. doi: 10.1038/s41467-022-32523-6.
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Intraductal patient-derived xenografts of estrogen receptor α-positive breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions.
雌激素受体 α 阳性乳腺癌的导管内患者源性异种移植物再现了人类病变的组织病理学谱和转移潜能。
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Accurate Control of 17β-Estradiol Long-Term Release Increases Reliability and Reproducibility of Preclinical Animal Studies.精确控制17β-雌二醇的长期释放可提高临床前动物研究的可靠性和可重复性。
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A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.一种 ERα 阳性乳腺癌的临床前模型指出,上皮微环境是决定腔面表型和激素反应的决定因素。
Cancer Cell. 2016 Mar 14;29(3):407-422. doi: 10.1016/j.ccell.2016.02.002. Epub 2016 Mar 3.
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World J Clin Oncol. 2014 Aug 10;5(3):412-24. doi: 10.5306/wjco.v5.i3.412.
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Metastasis dormancy in estrogen receptor-positive breast cancer.雌激素受体阳性乳腺癌的转移休眠。
Clin Cancer Res. 2013 Dec 1;19(23):6389-97. doi: 10.1158/1078-0432.CCR-13-0838.
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Mol Oncol. 2013 Oct;7(5):859-69. doi: 10.1016/j.molonc.2013.07.005. Epub 2013 Jul 12.