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

被引：74

作者：

Xu, Kun ^{[1
]}

Wang, Runtian ^{[1
]}

Xie, Hui ^{[2
]}

Hu, Longfei ^{[3
]}

Wang, Cong ^{[4
]}

Xu, Jiali ^{[1
]}

Zhu, Chengjun ^{[1
]}

Liu, Yiqiu ^{[1
]}

Gao, Fangyan ^{[1
]}

Li, Xintong ^{[1
]}

Wang, Cenzhu ^{[1
]}

Huang, Jinyi ^{[1
]}

Zhou, Wenbin ^{[2
]}

Zhou, Guohua ^{[5
]}

Shu, Yongqian ^{[1
]}

Guan, Xiaoxiang ^{[1
,6
]}

机构：

[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing, Peoples R China

[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Breast Surg, Nanjing, Peoples R China

[3] Singleron Biotechnol, Yaogu Ave 11, Nanjing, Jiangsu, Peoples R China

[4] Nanjing Med Univ, Affiliated Hosp 1, Dept Pathol, Nanjing, Peoples R China

[5] Nanjing Univ, Sch Med, Jinling Hosp, Dept Pharmacol, Nanjing, Peoples R China

[6] Nanjing Med Univ, Collaborat Innovat Ctr Personalized Canc Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Peoples R China

来源：

ONCOGENESIS | 2021年 / 10卷 / 10期

基金：

中国国家自然科学基金;

关键词：

CYSTATIN C; PROTEIN; GALECTIN-1; ACTIVATION; STC2;

D O I：

10.1038/s41389-021-00355-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：12

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