Tumor Entrained Neutrophils Inhibit Seeding in the Premetastatic Lung

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 c...

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Bibliographic Details
Published in:Cancer cell 2011-09, Vol.20 (3), p.300-314
Main Authors: Granot, Zvi, Henke, Erik, Comen, Elizabeth A., King, Tari A., Norton, Larry, Benezra, Robert
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Cells
Breast Neoplasms - immunology
Breast Neoplasms - pathology
Cell Line, Tumor
Chemokine CCL2 - metabolism
Cytotoxicity, Immunologic
Female
Granulocyte Colony-Stimulating Factor - metabolism
Humans
Hydrogen Peroxide - metabolism
Lung - immunology
Lung - pathology
Lung Neoplasms - immunology
Lung Neoplasms - pathology
Lung Neoplasms - secondary
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Molecular Sequence Data
Neoplasm Invasiveness
Neutrophils - immunology
Neutrophils - metabolism
Reactive Oxygen Species - metabolism
RNA Interference
RNA, Small Interfering
Transforming Growth Factor beta - metabolism
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Summary: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 2O 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. ► Tumor entrained neutrophils (TENs) accumulate in the premetastatic lung ► TENs provide antimetastatic protection by eliminating disseminated tumor cells ► Tumor-secreted factors are both required and sufficient for neutrophil entrainment ► Tumor-secreted TGF-β protects the primary tumor from neutrophil cytotoxicity
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2011.08.012