CD62Ldim Neutrophils Specifically Migrate to the Lung and Participate in the Formation of the Pre-Metastatic Niche of Breast Cancer

Frontiers in Oncology

Zhen Wang²  Wuzhen Chen²  Ke Su²  Chenghui Yang²  Jian Huang²  Jun Pan²  Zhigang Zhang³  Lili Li⁴  Fuming Qiu⁴  Jinfan Li⁵ 

[1] Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Department of Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;

关键词: breast cancer;    lung metastasis;    pre-metastatic niche;    neutrophil;    CD62L;    migration;   

DOI  :  10.3389/fonc.2020.540484

来源: DOAJ

【 摘 要 】

Lung metastasis is one of the leading causes of death in patients with breast cancer. The mechanism of tumor metastasis remains controversial. Recently, the formation of a pre-metastatic niche has been considered a key factor contributing to breast cancer metastasis, which might also explain the tendency of organ metastasis. Our study initially re-examined the critical time of the niche formation and simultaneously detected a novel subset of neutrophils, CD62Ldim neutrophils, which had not previously been reported in tumor metastasis; the number of these cells progressively increased during breast cancer progression and was closely related to the formation of the pre-metastatic niche. Furthermore, we explored the mechanism of their aggregation in the pre-metastatic niche in the lung and found that they were specifically chemoattracted by the CXCL12-CXCR4 signaling pathway. Compared to the CD62Lhi neutrophils, CD62Ldim neutrophils exhibited stronger adhesion and increased survival. The results provide new insights into the subsequent targeted treatment of breast cancer metastasis.

【 授权许可】

Unknown