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在肿瘤相关巨噬细胞模型中通过CRISPR/CAS9敲低CXCR4可减少人乳腺癌细胞迁移。

CXCR4 Knockdown Via CRISPR/CAS9 in a Tumor-Associated Macrophage Model Decreases Human Breast Cancer Cell Migration.

作者信息

Jaramillo-Valverde Luis, Levano Kelly S, Capristano Silvia, Tarazona David D, Cisneros Alberto, Yufra-Picardo Velia M, Valdivia-Silva Julio, Guio Heinner

机构信息

Biotechnology and Molecular Biology Laboratory, Instituto Nacional de Salud, Lima, PER.

Faculty of Health Sciences, Universidad de Huánuco, Huánuco, PER.

出版信息

Cureus. 2021 Dec 30;13(12):e20842. doi: 10.7759/cureus.20842. eCollection 2021 Dec.

DOI:10.7759/cureus.20842
PMID:35111484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8794389/
Abstract

Introduction Breast cancer is the leading cause of cancer-related deaths in women worldwide with the majority of deaths due to metastasis. The development of metastasis is closely related to the tumor microenvironment where tumor-associated macrophages (TAMs) are the main immune cell component playing a crucial role in tumor migration. Key players in tumor progression, metastasis and survival are the receptor CXCR4 and its ligand CXCL12. CXCR4 is expressed in multiple cell types including macrophages and breast cancer cells. Many studies have focus on the role of CXCR4 expressed in breast cancer cells. Methods In this study, we investigated the role of CXCR4 expressed in TAMs on breast cancer cell migration by reducing CXCR4 expression via CRISPR-CAS9 system in differentiated THP-1 cells (a TAMs model). Results According to wound healing migration assay, MCF7 cancer cells co-cultured with genetically edited dTHP-1 cells have a lower migration rate as compared to MCF7 cancer cells co-cultured with unedited and dTHP-1 cells. Conclusion The study demonstrates the role of CXCR4 on breast cancer cell migration through TAM-cancer cell crosstalk.

摘要

引言

乳腺癌是全球女性癌症相关死亡的主要原因，大多数死亡是由转移所致。转移的发生与肿瘤微环境密切相关，其中肿瘤相关巨噬细胞（TAM）是主要的免疫细胞成分，在肿瘤迁移中起关键作用。肿瘤进展、转移和生存的关键因素是受体CXCR4及其配体CXCL12。CXCR4在包括巨噬细胞和乳腺癌细胞在内的多种细胞类型中表达。许多研究聚焦于乳腺癌细胞中表达的CXCR4的作用。

方法

在本研究中，我们通过CRISPR-CAS9系统降低分化的THP-1细胞（一种TAM模型）中CXCR4的表达，研究TAM中表达的CXCR4对乳腺癌细胞迁移的作用。

结果

根据伤口愈合迁移试验，与未编辑的dTHP-1细胞共培养的MCF7癌细胞相比，与基因编辑的dTHP-1细胞共培养的MCF7癌细胞迁移率更低。

结论

该研究通过TAM-癌细胞间的相互作用证明了CXCR4对乳腺癌细胞迁移的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fe/8794389/e6ec1c04afdb/cureus-0013-00000020842-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fe/8794389/8e0111ece099/cureus-0013-00000020842-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fe/8794389/f0a492956c5f/cureus-0013-00000020842-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fe/8794389/e6ec1c04afdb/cureus-0013-00000020842-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fe/8794389/8e0111ece099/cureus-0013-00000020842-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fe/8794389/f0a492956c5f/cureus-0013-00000020842-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fe/8794389/e6ec1c04afdb/cureus-0013-00000020842-i03.jpg

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The role of chemokines in breast cancer pathology and its possible use as therapeutic targets.趋化因子在乳腺癌病理学中的作用及其作为治疗靶点的可能用途。
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