RRC ID 53871
Author Hiratsuka S, Tomita T, Mishima T, Matsunaga Y, Omori T, Ishibashi S, Yamaguchi S, Hosogane T, Watarai H, Omori-Miyake M, Yamamoto T, Shibata N, Watanabe A, Aburatani H, Tomura M, High KA, Maru Y.
Title Hepato-entrained B220+CD11c+NK1.1+ cells regulate pre-metastatic niche formation in the lung.
Journal EMBO Mol Med
Abstract 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 IFNγ induction. These findings indicate that liver-primed B220+CD11c+NK1.1+ cells suppress lung metastasis.
Volume 10(7)
Published 2018-7-1
DOI 10.15252/emmm.201708643
PII emmm.201708643
PMID 29930175
PMC PMC6034134
MeSH Animals CD11 Antigens Female Fibrinogen / metabolism Flow Cytometry Humans Interferon-gamma / immunology Killer Cells, Natural / immunology* Leukocyte Common Antigens Liver / immunology Liver / pathology* Lung / immunology Lung / pathology* Lung Neoplasms / immunology Lung Neoplasms / pathology* Lung Neoplasms / secondary Male Mice Neoplasm Metastasis* Precancerous Conditions*
IF 8.821
Times Cited 1
Mice RBRC00267