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Review
. 2019 Jun:110:69-76.
doi: 10.1016/j.molimm.2017.12.013.

Neutrophils: Homing in on the myeloid mechanisms of metastasis

Joshua Leach  1 , Jennifer P Morton  2 , Owen J Sansom  3
Affiliations
Review

Neutrophils: Homing in on the myeloid mechanisms of metastasis

Joshua Leach et al. Mol Immunol. 2019 Jun.

Abstract

The metastasis cascade is complex and comprises several stages including local invasion into surrounding tissue, intravasation and survival of tumour cells in the circulation, and extravasation and colonisation of a distant site. It is increasingly clear that these processes are driven not only by signals within the tumour cells, but are also profoundly influenced by stromal cells and signals in the tumour microenvironment. Amongst the many cell types within the tumour microenvironment, immune cells such as lymphocytes, macrophages and neutrophils play a prominent role in tumour development and progression. Neutrophils, however, have only recently emerged as important players, particularly in metastasis. Here we review the current evidence suggesting a multi-faceted role for neutrophils in the metastatic cascade.

Keywords: Epithelial cancer; Metastasis; Myeloid cells; Neutrophils; Tumour microenvironment.

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Figures

Fig. 1
Fig. 1
The role of neutrophils in the early metastatic cascade – primary tumour progression and invasion. NE, neutrophil elastase; Arg1, arginase 1; TGFβ, Transforming growth factor beta; EMT, epithelial-mesenchymal transition; Zeb1, Zinc finger E-box-binding homeobox 1; Twist, Twist-related protein 1; MMP, matrix metalloproteinase; ECM, extracellular matrix; VEGF, Vascular endothelial growth factor; HOCL, Hypochlorous acid; TIMP, tissue inhibitor of metalloproteinases; ADAMs, a disintegrin and metalloproteinase; G-CSF, Granulocyte-colony stimulating factor; CXCL, Chemokine (C-X-C motif) ligand; CCL, Chemokine (C-C motif) ligand; VE-cadherin, vascular endothelial cadherin.
Fig. 2
Fig. 2
The role of neutrophils in the late stages of the metastatic cascade – intravascular dissemination, extravasation, and metastasis growth. NETs, neutrophil extracellular traps; MMP, matrix metalloproteinase; ICAM-1, intercellular adhesion molecule 1; RAGE, receptor for advanced glycation endproducts; TLR, toll-like receptor; IRS-1, insulin receptor substrate 1; MET, mesenchymal-epithelial transition; IL-1β, interleukin 1 beta; MAPK, mitogen-activated protein kinase signalling; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PI3K, Phosphatidylinositol-4,5-bisphosphate 3-kinase signalling.
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