Neutrophil Extracellular Traps Promote Pancreatic Cancer Progression via the STING Pathway

Background: Pancreatic cancer is very susceptible to metastasis with a high mortality. Neutrophil extracellular traps (NETs) have been reported to be associated with poor prognosis in patients suffering from pancreatic cancer. However, the underlying mechanisms by which NETs facilitate cancer progression remain poorly understood. Methods: The expression of NETs was assessed in pancreatic cancer tissues and plasma samples from patients. Neutrophils were isolated from the blood of individuals diagnosed with pancreatic cancer to evaluate NETs formation. The impact of NETs on the progression of pancreatic cancer cells was investigated, along with a series of experiments aimed at elucidating the interaction mechanisms between neutrophils and cancer cells. Results: Pancreatic cancer samples had higher levels of NETs, and NETs formation was intensified in neutrophils derived from patients. NETs significantly promoted both migration and invasion capabilities in pancreatic cancer cells. Furthermore, the stimulator of interferon genes (STING) signaling pathway was stimulated to produce interleukin-8 (IL-8), which subsequently recruited more neutrophils and mediated further formation of NETs. Conclusions: Our data indicate a NETs-cancer aggressive crosstalk in pancreatic cancer. Specifically, NETs stimulate tumor cells to secrete IL-8, thereby promoting NETosis within the tumor microenvironment. Consequently, NETs may be a key target for pancreatic cancer treatment.