| First Author | Wu CF | Year | 2015 |
| Journal | Int J Cancer | Volume | 137 |
| Issue | 4 | Pages | 837-47 |
| PubMed ID | 25604426 | Mgi Jnum | J:222598 |
| Mgi Id | MGI:5644913 | Doi | 10.1002/ijc.29444 |
| Citation | Wu CF, et al. (2015) The lack of type I interferon induces neutrophil-mediated pre-metastatic niche formation in the mouse lung. Int J Cancer 137(4):837-47 |
| abstractText | Metastases are the major cause of death from cancer. Thus, understanding the regulation of metastatic processes is of utmost importance. Here we show that mice with impaired type I IFN signaling (Ifnar1(-/-) ) develop more lung metastases in the 4T1 mammary and LLC lung carcinoma model, compared to control mice. In Ifnar1(-/-) mice, higher metastasis load is accompanied by massive neutrophil accumulation in lungs. Elevated G-CSF levels in serum and enhanced CXCR2 expression on neutrophils are most likely responsible for this phenomenon. Lung infiltrating neutrophils facilitate an improved pre-metastatic niche formation, supporting more efficient tumor cell extravasation and proliferation in this organ. This is due to the enhanced expression of pro-metastatic proteins, like Bv8, MMP9, S100A8 and S100A9. Development of pre-metastatic niche together with reduced neutrophil cytotoxicity against tumor cells results in enhanced metastatic processes in Ifnar1(-/-) mice. Overall, our findings describe a novel role for IFN during metastasis development and suggest that new treatment strategies should be considered for prevention of metastasis formation in patients. |
