The role of neoangiogenesis in progression of solid tumors is crucial [Han J.M., 2017]. Activated neutrophils (Nph) can synthesize vascular endothelial growth factor (VEGF) and interleukine-8 (IL-8) [Merritt W.M., 2008], regulated by nuclear factor-kappa B (NF-κB) [Annunziata C.M., 2010]. The aim of the study was to assess the role of pro-angiogenic factors of circulating Nph in the progression of ovarian cancer (OC).
We isolated circulating Nph from the peripheral blood of 97 OC patients (stage I-IV FIGO) 36-76 years old on a double layer of ficoll-urographin. Using ELISA, the VEGF-A (RayBiotech, USA) and IL-8 (Vector-Best-Volga CJSC, Russia) levels were determined in the Nph lysate, and the expression of NF-kB (eBioscience, USA) was determined in the Nph nuclear fraction. The control group included 30 healthy women 23-65 years old. The study was conducted in accordance with the requirements of the IMEPC ULSU ethics commission (protocol №3 from 15.03.2015). The correlation between the parameters was evaluated using the Spearman coefficient, the statistical significance of the differences was evaluated using the nonparametric Mann-Whitney U-test (p ≤ 0.05).
We detected a statistically significant increase in the level of VEGF in Nph already at the initial stage of the OC compared to the control (469.764±185.028 pg/ml vs 50.483±9.505 pg/ml, p = 0.0053). With more advanced OC stage, the VEGF level in Nph decreased by 2 times, but remained statistically significantly high compared to control. An average correlation was revealed between the level of VEGF in Nph and the stage of OC (p = 0.5196). The level of NF-kB in the nuclear fraction of Nph was statistically significantly increased in I stage OC (0.589±0.129 mg/ml vs 0.166±0.028 mg/ml in the control, p = 0.0253) and decreased statistically significantly with the OC spread. A weak correlation between the level of NF-kB in Nph lyzate and the OC stage was revealed. The level of IL-8 in Nph did not significantly change in OC. An average correlation was found between the NF-kB level and IL-8 level in Nph (p = 0.6914).
The results obtained indicate an increase in the pro-angiogenic activity of circulating Nph with the progression of OC.
The authors.
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All authors have declared no conflicts of interest.