Polymorphonuclear Neutrophils and Tumors: Friend or Foe?
The tumor microenvironment is a dynamic network which apart from cancer cells includes also cells of the immune system such as polymorphonuclear neutrophils. Neutrophils are implicated in the interaction with cancer cells and, due to their ability of secr
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Polymorphonuclear Neutrophils and Tumors: Friend or Foe? Magdalena Klink and Zofia Sulowska
Abstract The tumor microenvironment is a dynamic network which apart from cancer cells includes also cells of the immune system such as polymorphonuclear neutrophils. Neutrophils are implicated in the interaction with cancer cells and, due to their ability of secreting the variety of active proteins and factors, play an important role in tumor progression and/or tumor destruction. In the tumor environment, neutrophils exist as anti-tumor phenotype (N1) and pro-tumoral phenotype (N2), analogous to the polarization of tumor-associated macrophages. The N1 phenotype of neutrophils is characterized by a cytotoxic and pro-inflammatory activity, while the N2 phenotype of cells has strong immunosuppressive properties. During cancer progression and metastasis, neutrophils facilitate and intensify extravasation of tumor cells as a result of the release of neutrophil metalloproteinases and elastase, which destroy the components of extracellular matrix, thus helping tumor cells to go through the endothelial barrier. On the other hand, tumor cells have a strong impact on the functional activity of neutrophils, and by causing immune system suppression in the host organism they promote the progression of the cancer. This review summarizes the pro- and anti-tumoral activity of neutrophils as the result of their direct contact with cancer cells and the release of different active mediators.
List of Abbreviations BMs ECM G-CSF GM-CSF
Basement membranes Extracellular matrix Granulocyte colony-stimulating factor Granulocyte–macrophage colony-stimulating factor
M. Klink (*) • Z. Sulowska Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106 str, 93-232 Lodz, Poland e-mail: [email protected] M. Klink (ed.), Interaction of Immune and Cancer Cells, DOI 10.1007/978-3-7091-1300-4_7, © Springer-Verlag Wien 2014
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huGCP-2 ICAM-1 IFN IL IRAK 1 IRS-1 MIP-1 α MMP NE NK NN PI3K ROS TAMs TANs TGF-β TLRs TNF-α TRAIL VCAM-1 VEGF
Human granulocyte chemotactic protein 2 Intracellular adhesion molecule 1 Interferon Interleukin Interleukin-1 receptor-associated kinase 1 Insulin receptor substrate-1 Macrophage inflammatory protein-1 α Metalloproteinase Neutrophil elastase Natural killer Naive neutrophils Phosphatidylinositol-3 kinase Reactive oxygen species Tumor-associated macrophages Tumor-associated neutrophils Transforming growth factor β Toll-like receptors Tumor necrosis factor-α TNF-related apoptosis-inducing ligand Vascular cell adhesion molecule-1 Vascular endothelial growth factor
Contents 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 Tumor-Associated Neutrophils: N1–N2 Polarization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3 Anti-tumoral Effect of TANs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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