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在转移性三阴性乳腺癌（TNBC）小鼠模型中通过表观遗传调控减少转移

Reduction of Metastasis via Epigenetic Modulation in a Murine Model of Metastatic Triple Negative Breast Cancer (TNBC).

作者信息

Zylla Jessica L S, Hoffman Mariah M, Plesselova Simona, Bhattacharya Somshuvra, Calar Kristin, Afeworki Yohannes, de la Puente Pilar, Gnimpieba Etienne Z, Miskimins W Keith, Messerli Shanta M

机构信息

Department of Biomedical Engineering, University of South Dakota, Sioux Falls, SD 57107, USA.

2-Dimensional Materials for Biofilm Engineering Science and Technology (2DBEST) Center, Sioux Falls, SD 57107, USA.

出版信息

Cancers (Basel). 2022 Mar 30;14(7):1753. doi: 10.3390/cancers14071753.

DOI:10.3390/cancers14071753
PMID:35406526
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8996906/
Abstract

This study investigates the effects of a dual selective Class I histone deacetylase (HDAC)/lysine-specific histone demethylase 1A (LSD1) inhibitor known as 4SC-202 (Domatinostat) on tumor growth and metastasis in a highly metastatic murine model of Triple Negative Breast Cancer (TNBC). 4SC-202 is cytotoxic and cytostatic to the TNBC murine cell line 4T1 and the human TNBC cell line MDA-MB-231; the drug does not kill the normal breast epithelial cell line MCF10A. Furthermore, 4SC-202 reduces cancer cell migration. In vivo studies conducted in the syngeneic 4T1 model, which closely mimics human TNBC in terms of sites of metastasis, reveal reduced tumor burden and lung metastasis. The mechanism of action of 4SC-202 may involve effects on cancer stem cells (CSC) which can self-renew and form metastatic lesions. Approximately 5% of the total 4T1 cell population grown in three-dimensional scaffolds had a distinct CD44/CD24 CSC profile which decreased after treatment. Bulk transcriptome (RNA) sequencing analyses of 4T1 tumors reveal changes in metastasis-related pathways in 4SC-202-treated tumors, including changes to expression levels of genes implicated in cell migration and cell motility. In summary, 4SC-202 treatment of tumors from a highly metastatic murine model of TNBC reduces metastasis and warrants further preclinical studies.

摘要

本研究调查了一种名为4SC-202（多马司他）的双重选择性I类组蛋白去乙酰化酶（HDAC）/赖氨酸特异性组蛋白去甲基化酶1A（LSD1）抑制剂对三阴性乳腺癌（TNBC）高转移小鼠模型中肿瘤生长和转移的影响。4SC-202对TNBC小鼠细胞系4T1和人TNBC细胞系MDA-MB-231具有细胞毒性和细胞生长抑制作用；该药物不会杀死正常乳腺上皮细胞系MCF10A。此外，4SC-202可减少癌细胞迁移。在同基因4T1模型中进行的体内研究（该模型在转移部位方面与人类TNBC非常相似）显示肿瘤负担和肺转移减少。4SC-202的作用机制可能涉及对癌症干细胞（CSC）的影响，癌症干细胞能够自我更新并形成转移病灶。在三维支架中生长的4T1细胞总数中约5%具有独特的CD44/CD24 CSC特征，治疗后该特征有所下降。对4T1肿瘤进行的大量转录组（RNA）测序分析显示，在4SC-202处理的肿瘤中，与转移相关的信号通路发生了变化，包括与细胞迁移和细胞运动相关的基因表达水平的变化。总之，用4SC-202治疗TNBC高转移小鼠模型中的肿瘤可减少转移，值得进一步开展临床前研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/bf50dad9cf23/cancers-14-01753-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/286801251e63/cancers-14-01753-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/2d336aa3922a/cancers-14-01753-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/d614ddf1f902/cancers-14-01753-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/0c0cdc026626/cancers-14-01753-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/bf50dad9cf23/cancers-14-01753-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/286801251e63/cancers-14-01753-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/2aa2b9522fd5/cancers-14-01753-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/90694c0a0cd1/cancers-14-01753-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/6ee9f11ee22b/cancers-14-01753-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/2d336aa3922a/cancers-14-01753-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/d614ddf1f902/cancers-14-01753-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/0c0cdc026626/cancers-14-01753-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9946/8996906/bf50dad9cf23/cancers-14-01753-g008.jpg

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本文引用的文献

1
clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.clusterProfiler 4.0：用于解释组学数据的通用富集工具。
Innovation (Camb). 2021 Jul 1;2(3):100141. doi: 10.1016/j.xinn.2021.100141. eCollection 2021 Aug 28.
2
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Cancers (Basel). 2021 Aug 20;13(16):4199. doi: 10.3390/cancers13164199.
3
Bioinformatics analysis for the identification of key genes and long non-coding RNAs related to bone metastasis in breast cancer.
A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance.
关于 LSD1 及其抑制剂在乳腺癌中的研究现状综述：分子机制与治疗意义
Front Pharmacol. 2022 Sep 16;13:989575. doi: 10.3389/fphar.2022.989575. eCollection 2022.
4
Differential molecular mechanistic behavior of HDACs in cancer progression.在癌症进展中 HDAC 的差异分子机制行为。
Med Oncol. 2022 Aug 16;39(11):171. doi: 10.1007/s12032-022-01770-4.
5
HDAC Class I Inhibitor Domatinostat Preferentially Targets Glioma Stem Cells over Their Differentiated Progeny.组蛋白去乙酰化酶 I 类抑制剂罗米地辛优先靶向神经胶质瘤干细胞而非其分化后代。
Int J Mol Sci. 2022 Jul 22;23(15):8084. doi: 10.3390/ijms23158084.
用于鉴定与乳腺癌骨转移相关的关键基因和长链非编码RNA的生物信息学分析
Aging (Albany NY). 2021 Jul 5;13(13):17302-17315. doi: 10.18632/aging.203211.
4
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Oral Dis. 2022 Nov;28(8):2139-2148. doi: 10.1111/odi.13860. Epub 2021 May 4.
5
Systematic comparison and assessment of RNA-seq procedures for gene expression quantitative analysis.系统比较和评估 RNA-seq 程序进行基因表达定量分析。
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6
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7
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8
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9
Triple-negative breast cancer molecular subtyping and treatment progress.三阴性乳腺癌分子分型及治疗进展。
Breast Cancer Res. 2020 Jun 9;22(1):61. doi: 10.1186/s13058-020-01296-5.
10
Tumorigenic and Metastatic Role of CD44/CD24 Cells in Luminal Breast Cancer.CD44/CD24细胞在腔面型乳腺癌中的致瘤和转移作用
Cancers (Basel). 2020 May 14;12(5):1239. doi: 10.3390/cancers12051239.