Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis

Molecular mechanisms underlying breast cancer lymph node metastasis remain unclear. Using single-cell sequencing, we investigated the transcriptome profile of 96,796 single cells from 15 paired samples of primary tumors and axillary lymph nodes. We identified nine cancer cell subclusters including C...

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Vydáno v:Oncogenesis (New York, NY) Ročník 10; číslo 10; s. 66 - 12
Hlavní autoři: Xu, Kun, Wang, Runtian, Xie, Hui, Hu, Longfei, Wang, Cong, Xu, Jiali, Zhu, Chengjun, Liu, Yiqiu, Gao, Fangyan, Li, Xintong, Wang, Cenzhu, Huang, Jinyi, Zhou, Wenbin, Zhou, Guohua, Shu, Yongqian, Guan, Xiaoxiang
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 05.10.2021
Nature Publishing Group
Témata:
38/39
631/67/1347
631/67/2329
Aldehyde dehydrogenase
Apoptosis
Breast cancer
CD44 antigen
Cell Biology
Human Genetics
Internal Medicine
Lymph nodes
Lymphatic system
Medicine
Medicine & Public Health
Metastases
Metastasis
Molecular modelling
Oncology
Stem cells
Transcriptomes
Tumor microenvironment
Tumors
ISSN:2157-9024, 2157-9024
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Shrnutí:Molecular mechanisms underlying breast cancer lymph node metastasis remain unclear. Using single-cell sequencing, we investigated the transcriptome profile of 96,796 single cells from 15 paired samples of primary tumors and axillary lymph nodes. We identified nine cancer cell subclusters including CD44 + / ALDH2 + /ALDH6A1 + breast cancer stem cells (BCSCs), which had a copy-number variants profile similar to that of normal breast tissue. Importantly, BCSCs existed only in primary tumors and evolved into metastatic clusters infiltrating into lymph nodes. Furthermore, transcriptome data suggested that NECTIN2-TIGIT-mediated interactions between metastatic breast cancer cells and tumor microenvironment (TME) cells, which promoted immune escape and lymph node metastasis. This study is the first to delineate the transcriptome profile of breast cancer lymph node metastasis using single-cell RNA sequencing. Our findings offer novel insights into the mechanisms underlying breast cancer metastasis and have implications in developing novel therapies to inhibit the initiation of breast cancer metastasis.
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ISSN:2157-9024
2157-9024
DOI:10.1038/s41389-021-00355-6