title: The lack of type I interferon induces neutrophil-mediated pre-metastatic niche formation in the mouse lung.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan.|Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124, Braunschweig, Germany.
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Wu
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124, Braunschweig, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Andzinski
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124, Braunschweig, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kasnitz
authors.affiliation: Innate Immunity and Infection Group, Department of Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124, Braunschweig, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kröger
authors.affiliation: Bioinformatics and Statistics Group, Department of Cellular Proteomics, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124, Braunschweig, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Klawonn
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124, Braunschweig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124, Braunschweig, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124, Braunschweig, Germany.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Jablonska
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics*; D009504:Neutrophils / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis; D015398:Signal Transduction
chemical_list: D007370:Interferon Type I; D023063:Receptors, Interleukin-8B; D016179:Granulocyte Colony-Stimulating Factor
keywords: interferon; metastasis; neutrophils; premetastatic niche