Table 1 Key NET stimuli involved in cancer progression. References are annotated to indicate whether NETotic effect has been shown in human (H) neutrophils, mouse (M) neutrophils, or both (HM)
Stimulus/model: | Relevance to cancer progression: | Origin: |
|---|---|---|
May simulate response to infection; repeated intranasal dosage in mice activated dormant cancer cells and enhanced metastatic proliferation | Gram-negative bacteria | |
N/A | Synthetic/pharmaceutical | |
Platelet-activating factor [19]M | Promotes tumor cell proliferation, neovascularization, and immunosuppressive phenotype | Leukocyte, platelet, and endothelial secretion in inflammation |
Associates with existing NETs; role in platelet and neutrophil activation; synergizes with LPS and thus may exacerbate response to infection | Leukocyte and platelet secretion in inflammation; expressed in some tumors; released during cell death | |
Drives neutrophilia; positive correlation with poor outcome in women with breast cancer | Expressed in some tumors; released from activated endothelial cells | |
Drives neutrophilia; positive correlation with metastasis; potentiates extracellular vesicle driven NETosis | Expressed in some tumors | |
Catalyzes histone citrullination; inhibition prevents NETosis in most circumstances | Neutrophils; expressed in some tumors | |
P-selectin [41]M | Facilitates neutrophil motility; drives platelet-neutrophil aggregation | Endothelial cells; platelets |
Activates platelets which activate neutrophils and causes NETosis, potentially through multiple pathways | Secreted during NETosis; expressed in some tumors; contained in tumor EVs | |
Tumor EVs [21]M | May influence neutrophil behavior once taken up; contain inflammatory cytokines and are vital to oncogenic signaling; prothrombotic | Released from tumor cells |