Details

Autor(en) / Beteiligte

• Granot, Zvi
• Henke, Erik
• Comen, Elizabeth A.
• King, Tari A.
• Norton, Larry
• Benezra, Robert

Titel

Tumor Entrained Neutrophils Inhibit Seeding in the Premetastatic Lung

Ist Teil von

• Cancer cell, 2011-09, Vol.20 (3), p.300-314

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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