Angiogenic potential of circulating blood neutrophils in endometrial cancer

Abstract

Neutrophils play an important role in carcinogenesis, mediating inflammation, immunosuppression and metastasis. A dual role of neutrophils in regulation of angiogenesis has been shown. Endometrial cancer is the most common malignant neoplasm of the female reproductive system. To assess the cellular angiogenic potential, we determined the levels of inflammatory and angiogenic cytokines (VEGF-A, IL-17A, IL-1β, IL-6) in cell lysate of peripheral blood neutrophils in the patients with endometrial cancer, and with uterine myoma (comparison group). Expression of the nuclear factor-kB was determined. In nuclear fraction of neutrophils. The neutrophil-to-lymphocyte ratio (NLR) was assessed in the studied groups. Statistical processing of the obtained data was carried out using Statistica 10 software. We have not found any significant changes in NLR in endometrial cancer, compared with controls and the uterine myoma groups. Expression of NF-kB and VEGF was increased as compared to the control for all the studied stages of endometrial cancer and in uterine myoma. There was a change in NF-kB level in neutrophils, depending on the tumor differentiation grade. A regression relationship was found between the content of VEGF and NF-kB in neutrophils. We have found increased IL-1β and IL-6 levels in neutrophils of the uterine myoma patients, and at different stages of endometrial cancer compared with control. The IL-1β level was higher in neutrophils of the patients with intermediate and high tumor grade, compared to low-grade cases. IL-17A expression in the neutrophil lysate was significantly reduced in uterine myoma and at different stages of endometrial cancer, as compared with controls. There was a moderate inverse correlation between the contents of VEGF and IL-6 in neutrophils (r = -0.426, p = 0.001); a remarkable inverse relationship between VEGF and IL-17A (r = -0.615, p < 0.001). The combination of IL-6 and IL-17A levels in the neutrophils lysate (according to the results of multivariate analysis) may be used for the differential diagnosis of endometrial cancer and uterine myoma. Thus, the differences in the expression of inflammatory and angiogenic cytokines included in NF-kB-dependent signaling, may point to acquisition of pro-tumor functions by neutrophils during the endometrial cancer progression.

Keywords

• endometrial cancer
• myoma
• neutrophils
• vegf-a
• il-17a
• il-1β
• il-6
• nf-kb-signaling
• angiogenesis