Dataset Information

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

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.

SUBMITTER: Wang Z

PROVIDER: S-EPMC7593663 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

CD62L<sup>dim</sup> Neutrophils Specifically Migrate to the Lung and Participate in the Formation of the Pre-Metastatic Niche of Breast Cancer.

Wang Zhen Z Yang Chenghui C Li Lili L Zhang Zhigang Z Pan Jun J Su Ke K Chen Wuzhen W Li Jinfan J Qiu Fuming F Huang Jian J

Frontiers in oncology 20201015

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, CD62L<sup>dim</sup> neutrophils, which ha ...[more]

PMID: 33178575

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Project description:The pre-metastatic niche has been shown to play a critical role in tumor metastasis, and its formation is closely related to the tumor microenvironment. However, the underlying molecular mechanisms remain unclear. In the present study, we successfully established a mouse model of lung metastasis using luciferase-expressing MDA-MB-435s cells. In this model, recruitment of vascular endothelial growth factor receptor-1 (VEGFR1)+CD133+ hematopoietic progenitor cells (HPCs) was gradually increased in lung but gradually decreased after the formation of tumor colonies in lung. We also established a highly metastatic MDA-MB-435s (MDA-MB-435s-HM) cell line from the mouse model. Changes in protein profiles in different culture conditions were investigated by protein microarray analysis. The levels of CXC chemokine ligand 16, interleukin (IL)-2R?, IL-2R?, matrix metalloproteinase (MMP)-1, MMP-9, platelet-derived growth factor receptor (PDGFR)-?, stromal cell-derived factor (SDF)-1?, transforming growth factor (TGF)-?, platelet endothelial cell adhesion molecule (PECAM)-1 and vascular endothelial (VE)-cadherin were significantly greater (>?fivefold) in the culture medium from MDA-MB-435s-HM cells than in that from MDA-MB-435s cells. Moreover, the levels of MMP-9, PDGFR-?, and PECAM-1 were significantly greater in the co-culture medium of MDA-MB-435s-HM cells and CD133+ HPCs than in that from MDA-MB-435s-HM cells. Differentially expressed proteins were validated by enzyme-linked immunosorbent assay, and expression of their transcripts was confirmed by quantitative real-time polymerase chain reaction. Moreover, inhibition of MMP-9, PDGFR-?, and PECAM-1 by their specific inhibitors or antibodies significantly decreased cell migration, delayed lung metastasis, and decreased recruitment of VEGFR1+CD133+ HPCs into lung. Intra-hepatic growth of HPCs enhanced the invasive growth of MDA-MB-435s-HM cells in the liver. Our data indicate that VEGFR1+CD133+ HPCs contribute to lung metastasis.

Dataset Information

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

Publications

CD62L<sup>dim</sup> Neutrophils Specifically Migrate to the Lung and Participate in the Formation of the Pre-Metastatic Niche of Breast Cancer.

Similar Datasets

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