Tumor entrained neutrophils inhibit seeding in the premetastatic lung

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • RNA Interference
  • RNA, Small Interfering
  • Reactive Oxygen Species / metabolism
  • Transforming Growth Factor beta / metabolism


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Transforming Growth Factor beta
  • Granulocyte Colony-Stimulating Factor
  • Hydrogen Peroxide

Associated data

  • GEO/GSE30888