AUTHOR=Wang Zhen , Yang Chenghui , Li Lili , Zhang Zhigang , Pan Jun , Su Ke , Chen Wuzhen , Li Jinfan , Qiu Fuming , Huang Jian TITLE=CD62Ldim Neutrophils Specifically Migrate to the Lung and Participate in the Formation of the Pre-Metastatic Niche of Breast Cancer JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.540484 DOI=10.3389/fonc.2020.540484 ISSN=2234-943X ABSTRACT=

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.