[PDF][PDF] Tumor entrained neutrophils inhibit seeding in the premetastatic lung

Z Granot, E Henke, EA Comen, TA King, L Norton… - Cancer cell, 2011 - cell.com
Z Granot, E Henke, EA Comen, TA King, L Norton, R Benezra
Cancer cell, 2011cell.com
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 …
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 H2O2 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.
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