Neutrophil extracellular traps in gastrointestinal cancer

Abstract

Gastrointestinal (GI) cancer is a high-risk malignancy and is characterized by high mortality and morbidity worldwide. Neutrophil extracellular traps (NETs), a weblike structure consisting of chromatin DNA with interspersed cytoplasmic and granule proteins, are extruded by activated neutrophils to entrap and kill bacteria and fungi. However, accumulating evidence shows that NETs are related to the progression and metastasis of cancer. In clinical studies, NETs infiltrate primary GI cancer tissues and are even more abundant in metastatic lesions. The quantity of NETs in peripheral blood is revealed to be associated with ascending clinical tumour stages, indicating the role of NETs as a prognostic markers in GI cancer. Moreover, several inhibitors of NETs or NET-related proteins have been discovered and used to exert anti-tumour effects in vitro or in vivo, suggesting that NETs can be regarded as targets in the treatment of GI cancer. In this review, we will focus on the role of NETs in gastric cancer and colorectal cancer, generalizing their effects on tumour-related thrombosis, invasion and metastasis. Recent reports are also listed to show the latest evidences of how NETs affect GI cancer. Additionally, notwithstanding the scarcity of systematic studies elucidating the underlying mechanisms of the interaction between NETs and cancer cells, we highlight the potential importance of NETs as biomarkers and anti-tumour therapeutic targets.

Keywords: Neutrophil extracellular traps; Gastric cancer; Colorectal cancer; Biomarkers; Therapeutic targets

Core Tip: Neutrophil extracellular traps (NETs) have been reported to participate in progression and metastasis in gastrointestinal (GI) cancer. Recent reports demonstrate that NET formation is enhanced in GI cancer patients as well as some mouse models and that elevated levels of NETs indicate an adverse outcome in patients. Furthermore, NETs can trap disseminated cancer cells and assist the formation of metastatic lesions although the underlying mechanisms remain vague. More studies are needed before NETs can be used as reliable biomarkers and therapeutic targets in GI cancer.