| First Author | Hiratsuka S | Year | 2018 |
| Journal | EMBO Mol Med | Volume | 10 |
| Issue | 7 | PubMed ID | 29930175 |
| Mgi Jnum | J:308958 | Mgi Id | MGI:6511404 |
| Doi | 10.15252/emmm.201708643 | Citation | Hiratsuka S, et al. (2018) Hepato-entrained B220(+)CD11c(+)NK1.1(+) cells regulate pre-metastatic niche formation in the lung. EMBO Mol Med 10(7) |
| abstractText | Primary tumours establish metastases by interfering with distinct organs. In pre-metastatic organs, a tumour-friendly microenvironment supports metastatic cells and is prepared by many factors including tissue resident cells, bone marrow-derived cells and abundant fibrinogen depositions. However, other components are unclear. Here, we show that a third organ, originally regarded as a bystander, plays an important role in metastasis by directly affecting the pre-metastatic soil. In our model system, the liver participated in lung metastasis as a leucocyte supplier. These liver-derived leucocytes displayed liver-like characteristics and, thus, were designated hepato-entrained leucocytes (HepELs). HepELs had high expression levels of coagulation factor X (FX) and vitronectin (Vtn) and relocated to fibrinogen-rich hyperpermeable regions in pre-metastatic lungs; the cells then switched their expression from Vtn to thrombospondin, both of which were fibrinogen-binding proteins. Cell surface marker analysis revealed that HepELs contained B220(+)CD11c(+)NK1.1(+) cells. In addition, an injection of B220(+)CD11c(+)NK1.1(+) cells successfully eliminated fibrinogen depositions in pre-metastatic lungs via FX Moreover, B220(+)CD11c(+)NK1.1(+) cells demonstrated anti-metastatic tumour ability with IFNgamma induction. These findings indicate that liver-primed B220(+)CD11c(+)NK1.1(+) cells suppress lung metastasis. |
