Metastatic potential of NET in neoplastic disease

Abstract

In response to various stimuli, neutrophils and eosinophils can release neutrophil extracellular traps (NET) consisting of proteolytic enzymes, DNA and other components of the cell nucleus. The NETosis process has been characterized as a mechanism of programmed cell death, which leads to chromatin decondensation and disintegration of organelles, followed by lysis of the cell membrane. In recent years the significant role of neutrophils in the pathogenesis of cancer has been highlighted. The presence of two subpopulations of TAN with different phenotypes and functions - acting antitumor "N1" and the pro-cancerous "N2" - has been discovered. By the release of cytokines and chemokines neutrophils may affect angiogenesis and contribute to escape of tumor cells from immune surveillance. Interactions between cells and the microenvironment are of vital importance both for the preservation of homeostasis in normal tissue and tumor growth. They affect the initiation of disease progression and prognosis. The impact of NETosis on the process of metastasis is evaluated in the context of the functions of the individual components of the NET (MMP-9, CG, NE). Furthermore, presumably the pro- or anti-tumor effect of NETosis depends on many factors including the status of the immune system or tumor microenvironment. Probably the cancer cells can be captured by the NET microenvironment in the same manner as microorganisms. However, the high concentration of proteins released during NETosis can induce their proliferation and inhibit apoptosis, thus promoting tumor growth. A better understanding of NETosis function in tumor progression may lead to the emergence of new prognostic factors and targets for therapy in many types of cancer.