Lung resided monocytic myeloid-derived suppressor cells contribute to premetastatic niche formation by enhancing MMP-9 expression

Juechao Zhang; Xiaoqing Han; Huifang Shi; Yanyan Gao; Xuan Qiao; Huihan Li; Min Wei; Xianlu Zeng

doi:10.1016/j.mcp.2019.101498

Lung resided monocytic myeloid-derived suppressor cells contribute to premetastatic niche formation by enhancing MMP-9 expression

Mol Cell Probes. 2020 Apr:50:101498. doi: 10.1016/j.mcp.2019.101498. Epub 2019 Dec 28.

Authors

Juechao Zhang¹, Xiaoqing Han², Huifang Shi², Yanyan Gao³, Xuan Qiao², Huihan Li², Min Wei⁴, Xianlu Zeng⁵

Affiliations

¹ The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China; Jilin University, Changchun, China.
² The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
³ Jilin Agricultural University, Changchun, China.
⁴ The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China. Electronic address: weim750@nenu.edu.cn.
⁵ The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun, China. Electronic address: zengx779@nenu.edu.cn.

PMID: 31891749
DOI: 10.1016/j.mcp.2019.101498

Abstract

In cancer patients, the prevalence of myeloid-derived suppressor cells (MDSCs) is correlated with the degree of malignancy. In the present study, we investigated the role of circulating M-MDSCs in premetastatic niche formation using a mouse syngeneic tumor model and found that there was an increased frequency of M-MDSCs in the peripheral blood of tumor-bearing mice. M-MDSCs tracking and lung tissue histological analyses revealed that the malignant conditions promote the residence of circulating M-MDSCs and increased tumor cell arrest in the lungs. We further found that MMP-9 expression was increased in the circulating M-MDSCs and the administration of an MMP-9 inhibitor suppressed M-MDSCs transplantation-induced tumor cell arrest in the lung. Therefore, our findings suggest that the expansion of circulating M-MDSCs during tumor progression contributes to premetastatic niche formation by increasing MMP-9 expression.

Keywords: Matrix metalloprotein 9; Metastasis; Monocytic myeloid-derived suppressor cells; Pre-metastatic niche; Tumor progression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Immunosuppression Therapy
Lung / pathology*
Lung Neoplasms / blood
Lung Neoplasms / enzymology*
Lung Neoplasms / genetics
Lung Neoplasms / pathology*
Male
Matrix Metalloproteinase 9 / chemistry
Matrix Metalloproteinase 9 / metabolism*
Melanoma, Experimental / pathology
Mice, Inbred C57BL
Monocytes / pathology*
Myeloid-Derived Suppressor Cells / pathology*
Neoplasm Metastasis
Peptides / chemistry

Substances

Peptides
Matrix Metalloproteinase 9