Neutrophils participate in tumor progression by acting both at primary tumors and at the (pre)metastatic niche. (A) In primary tumors, neutrophils can mediate angiogenesis through the release of MMP9, S100A8/9, and BV8 to activate VEGF. The production of growth factors and laminin degradation by the neutrophil-derived proteases neutrophil elastase (NE) and MMP9 can assist tumor cell proliferation. Alternatively, inflammatory stimuli (IL-1β and TNF-α) can induce neutrophil MET expression and binding of HGF, leading to NO production and tumor cell killing. Neutrophils also use antibody-dependent cellular cytotoxicity (ADCC) to kill cancer cells. (B) Neutrophils can support metastasis through a number of different factors individually or in combination. Inflammation induced by molecules such as S100A8 increases vascular permeability and therefore extravasation. Direct interactions between cancer cells and neutrophils or NETs can lead to their arrest in the vasculature. In addition, NETs have been suggested to wake dormant tumor cells, and neutrophils can feed tumor cells with lipids to aid their survival. Together, these events favor tumor cell extravasation and metastasis. Neutrophils can also aid tumor cell killing. CCL2 produced by the primary tumor can activate neutrophils in the premetastatic niche to produce hydrogen peroxide, providing an efficient tumor cell killing mechanism. IFN-β has also been shown to increase neutrophil antitumor potential by increasing NET capacity and cytotoxicity toward tumor cells. (C) The release of ROS and NO can induce tumor cell death, but conversely, through ROS, NO, arginase (ARG), prostaglandin E₂ (PGE₂), or a “shielding” effect of NETs, neutrophils can suppress cytotoxic immune cell activity.