Table 1 The function of neutrophil proteins in cancer
Granule | Gene name | Protein name | Functions | References |
|---|---|---|---|---|
Azurophil (primary) neutrophil granules | AZU1 | Azurocidin | Antibacterial activity (Gram-bacteria); monocyte and fibroblast-specific chemotaxis; binds heparin; reprograms stellate cells toward a phenotype affecting the cancer microarchitecture; disrupts vascular endothelial cell morphology | |
DEFA1-4 | Neutrophil defensins | Antibacterial, fungicidal, and antiviral activities; enhance anticancer immunity; direct cytolysis(high concentration); induce apoptosis; inhibiting angiogenesis; stimulate cancer growth (low concentration); promotes invasiveness | ||
PRTN3 (MBN) | Myeloblastin | Serine protease; facilitates transendothelial neutrophil migration; PRTN3-involved IκBα cleavage leads to abnormal activation of NFκB signaling pathway (carcinogenesis); inhibits T cell proliferation; mediates cancer metastasis to bone | ||
CD63 (MLA1) | CD63 antigen | Cell surface receptor for TIMP1; induces NET formation; creates a premetastatic niche in the liver | ||
CTSG | Cathepsin G | Antimicrobial, serine protease; facilitates neutrophil anti-cancer cytotoxicity; induces cell migration and multicellular aggregation; promotes metastasis; impairs NKp46-mediated responses of NK cells | ||
ELA2 (ELANE) | Neutrophil elastase | Serine protease; facilitates primary cancer growth and secondary organ metastasis; selectively kills cancer cells and attenuates carcinogenesis; enhances cancer cell invasion; involved in awakening of dormant cancer cells; cleaves PML-RARα and is important for the development of APL in mice | ||
MPO | Myeloperoxidase | Microbicidal activity against a wide range of organisms; cancer cell cytotoxicity; awakening of dormant cancer cells by accumulation of oxidized lipids | ||
BPI | Cap57; bactericidal permeability-increasing protein | Antibacterial, anticancer, and LPS-neutralizing activities; cancer cell cytotoxicity | [77] | |
Specific (secondary) neutrophil granules | CHI3L1 | Chitinase-3-like protein 1 | Glycoside hydrolase family 18; binds to chitin, heparin, and hyaluronic acid; plays a critical role in cancer cell growth, proliferation, invasion, metastasis, angiogenesis, activation of tumor-associated macrophages, and Th2 polarization of CD4 + T cells | [78] |
NGAL (LCN2) | Lipocalin 2 | Antimicrobial; functions in innate immune defense; induces apoptosis of B lymphocytes; mediates appetite suppression; induces mesenchymal-epithelial transition of cancer cells thereby facilitating colonization and metastatic outgrowth | ||
LTF (GIG12) | Lactoferrin | Antimicrobial, anti-viral, antioxidant, anti-cancer, and anti-inflammatory activities; modulation of immune responses; anti-proliferation of cancer cell line; has a radiation resistance effect; LTF-IC can convert TAMs into M1-like cells | ||
Gelatinase (tertiary) neutrophil granules | MMP9 (CLG4B) | Matrix metalloproteinase-9 | Contributions to squamous carcinogenesis; required for cancer vasculogenesis; promotes angiogenesis and cancer invasion; involved in awakening of dormant cancer cells | |
FCN1 (FCNM) | Ficolin-1 | Pattern-recognition receptor in innate immunity; downregulated in cancer; not associated with cancer | ||
CAMP | Cathelicidin antimicrobial peptide | Antibacterial activity through binding LPS; cleaved into 2 antimicrobial peptides FALL-39 and LL-37; LL-37 plays a role in carcinogenesis; also displays anti-cancer effect | ||
MMP8 | Neutrophil collagenase | Inhibiting NET formation; inhibits cancer cell invasion, proliferation and metastasis | ||
Other neutrophil proteins | S100A8/A9 | S100-A8/A9 | Proinflammatory protein; inflammation and oxidative stress; induces activation of myeloperoxidase; induces the release of gelatinase and specific granules; enhances cancer cell survival and chemoresistance; stimulates the recruitment of myeloid cells leading to cancer growth, formation of premetastatic niche, and metastasis | |
ANXA1 | Annexin A1 | Anti-inflammation protein; associated with cancer progression and metastasis; required in transvascular pumping of solid cancer; required in chemotherapy-induced anticancer immunity of dendritic cells; promotes immune cells infiltration |