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Cancer Cell. 2011 Sep 13;20(3):300-14. doi: 10.1016/j.ccr.2011.08.012.

Tumor entrained neutrophils inhibit seeding in the premetastatic lung.

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Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.


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.

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