Potential role of neutrophil extracellular traps in ovarian cancer-associated venous thrombosis

Patients with ovarian cancer have an increased risk of venous thrombosis, but the mechanisms underlying ovarian cancer-associated venous thrombosis remain unclear. This study aimed to investigate the formation of intravascular neutrophil extracellular traps (NETs) and their pathological role in patients with ovarian cancer. Neutrophils isolated from peripheral blood were examined for NETs formation. Neutrophils from patients with ovarian cancer exhibited increased spontaneous NETs formation. Conditioned media from some ovarian cancer cell lines and sera from patients with ovarian cancer induced NETs formation in neutrophils from healthy donors, suggesting that tumor-derived factors promote NETs formation. Patients with ovarian cancer had higher serum granulocyte-colony stimulating factor (G-CSF), which induces NETs formation. Serum NETs levels were measured by sandwich ELISA. As a result, patients with ovarian cancer showed higher circulating NETs than patients with benign tumors. Clinical records of patients with ovarian cancer treated at our institution were retrospectively reviewed. High circulating NETs levels were associated with poor prognosis, venous thrombosis, and elevated platelet counts. Immunohistochemistry revealed NETs foci within thrombi of patients with ovarian cancer. In conclusion, ovarian cancer may predispose neutrophils to increased NETs formation, which may have a causal effect on venous thrombosis.