The involvement of neutrophil infiltration in the formation of lung pre-metastatic niche

Abstract

The pre-metastatic niche (PMN) formation is the critical step of cancer metastasis. Nowadays, the infiltration of immune cells was found in PMN, but their function is still unknown. We investigated types and functions of immune cell accumulated in lung PMN. The lung of MMTV-PyVT mouse at 9 weeks was used to be the model of lung PMN. Neutrophil, M-MDSCs and Tregs were isolated from the lungs of mice by antibody microbeads. Our studies showed that large number of neutrophil, but not Tregs or M-MDSCs, was found in the lung PMN (Fig.1A to 1C). Our result showed that neutrophils expressed higher levels of MMP-9 (Fig.2A). Furthermore, the higher ratio of neutrophil underwent NETosis in the lung of MMTV-PyVT mice was found (Fig.2B). We demonstrate that increased neutrophils infiltration, which expressed MMP-9 and undergo NETosis promotes the remodeling of lung microenvironment, resulting in cancer metastasis. Fig1. The neutrophil infiltration in lung PMN. The cell number of neutrophil (A), M-MDSCs (B) and Tregs (C) in the lung of mices. Fig2. neutrophil expressed MMP-9 and Netosis in the lung of mice. (A)The MMP-9 level. (B)Netosis of neutrophil in the lung.