title: Tumor entrained neutrophils inhibit seeding in the premetastatic lung.
abstract: Primary tumors have been shown to prepare distal organs for later colonization of metastatic cells by stimulating organ-specific infiltration of bone marrow derived cells. Here we demonstrate that neutrophils accumulate in the lung prior to the arrival of metastatic cells in mouse models of breast cancer. Tumor-entrained neutrophils (TENs) inhibit metastatic seeding in the lungs by generating H(2)O(2) and tumor secreted CCL2 is a critical mediator of optimal antimetastatic entrainment of G-CSF-stimulated neutrophils. TENs are present in the peripheral blood of breast cancer patients prior to surgical resection but not in healthy individuals. Thus, whereas tumor-secreted factors contribute to tumor progression at the primary site, they concomitantly induce a neutrophil-mediated inhibitory process at the metastatic site.
authors: Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
authors: Zvi
authors: Z
authors: Granot
authors: Erik
authors: E
authors: Henke
authors: Elizabeth A
authors: EA
authors: Comen
authors: Tari A
authors: TA
authors: King
authors: Larry
authors: L
authors: Norton
authors: Robert
authors: R
authors: Benezra
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D016179:Granulocyte Colony-Stimulating Factor; D006861:Hydrogen Peroxide