Neutrophil extracellular traps in cancer progression

Abstract

Neutrophils are being increasingly recognized as an important element in tumor progression. They have been shown to exert important effects at nearly every stage of tumor progression with a number of studies demonstrating that their presence is critical to tumor development. Novel aspects of neutrophil biology have recently been elucidated and its contribution to tumorigenesis is only beginning to be appreciated. Neutrophil extracellular traps (NETs) are neutrophil-derived structures composed of DNA decorated with antimicrobial peptides. They have been shown to trap and kill microorganisms, playing a critical role in host defense. However, their contribution to tumor development and metastasis has recently been demonstrated in a number of studies highlighting NETs as a potentially important therapeutic target. Here, studies implicating NETs as facilitators of tumor progression and metastasis are reviewed. In addition, potential mechanisms by which NETs may exert these effects are explored. Finally, the ability to target NETs therapeutically in human neoplastic disease is highlighted.

Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis

“…Accumulating evidence indicates that solid tumors frequently display an inflammatory microenvironment [51,89], characterized by large numbers of tumor-associated neutrophils, which play an important role in cancer progression and angiogenesis [90][91][92]. The role of the crosstalk between cancer cells and stromal cells in tumor growth, metastasis, as well as response to antitumor therapy [93][94][95][96] and the tumor promoting activities of fibroblasts, which are the most abundant cells in the tumor stroma, are also well established [97].…”

The Complex Role of Neutrophils in Tumor Angiogenesis and Metastasis

“…In addition, Cools-Lartigue and colleagues reported that neutrophil-released neutrophil extracellular traps (NET) can contribute to cancer metastasis (94). NETs are neutrophil-derived structures composed of DNA, chromatin, and granule proteins and represent a host defense mechanism by trapping and killing microorganisms (95). Circulating tumor cells become trapped within NETs, and NET trapping increases formation of liver metastasis (94).…”

Neutrophil Extracellular Traps Accumulate in Peripheral Blood Vessels and Compromise Organ Function in Tumor-Bearing Animals

“…Another interesting observation in this context, connecting the coagulation and innate immune systems, is the fact that neutrophil extracellular traps (NET) have been found to play a role in malignant progression (6,7). NETs were identified in 2004 (8) and are extracellular networks that primarily consist of DNA released from neutrophils together with antimicrobial peptides and proteases derived from neutrophil granules.…”