mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-APO-2163mimmun-2163Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESАнгиогенный потенциал нейтрофилов циркулирующей крови при раке эндометрияAngiogenic potential of circulating blood neutrophils in endometrial cancerhttps://orcid.org/0000-0001-7559-5246АбакумоваТ. В.AbakumovaT. V.

к.б.н., доцент, доцент кафедры физиологии и патофизиологии,

432017, г. Ульяновск, ул. Архитектора Ливчака, 2

PhD (Biology), Associate Professor, Department of Physiology and Pathophysiology,

432017, Ulyanovsk, Arch. Livchak str., 2

taty-abakumova@yandex.ruhttps://orcid.org/0000-0002-5117-1382ГенингТ. П.GeningT. P.

д.б.н., профессор, заведующая кафедрой физиологии и патофизиологии,

г. Ульяновск

PhD, MD (Biology), Professor, Head, Department of Physiology and Pathophysiology,

Ulyanovsk 

Naum-53@yandex.ruhttps://orcid.org/0000-0001-6970-6659ГенингС. О.GeningS. O.

ассистент кафедры физиологии и патофизиологии,

г. Ульяновск

Assistant Professor, Department of Physiology and Pathophysiology,

Ulyanovsk 

sgening@bk.ruhttps://orcid.org/0000-0002-1525-2070АнтонееваИ. И.AntoneevaI. I.

д.м.н., доцент, профессор кафедры онкологии и лучевой диагностики;

заведующая гинекологическим отделением,

г. Ульяновск

PhD, MD (Medicine), Associate Professor, Professor, Department of Oncology and Radiology;

Head of the Gynecological Department, 

Ulyanovsk 

aii72@mail.ruФГБОУ ВО «Ульяновский государственный университет»РоссияUlyanovsk State UniversityRussian FederationФГБОУ ВО «Ульяновский государственный университет»; ГУЗ «Областной клинический онкологический диспансер»РоссияUlyanovsk State University; Ulyanovsk Regional Clinical Oncology CenterRussian Federation202124042021232339344Copyright © Абакумова Т.В., Генинг Т.П., Генинг С.О., Антонеева И.И., 20212021Абакумова Т.В., Генинг Т.П., Генинг С.О., Антонеева И.И.Abakumova T.V., Gening T.P., Gening S.O., Antoneeva I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2163

Нейтрофилы играют важную роль в канцерогенезе, опосредуя воспаление, иммуносупрессию и метастазирование, а также показана двоякая роль нейтрофилов в регуляции ангиогенеза. Рак эндометрия является наиболее распространенным злокачественным новообразованием женской репродуктивной системы. С целью оценки ангиогенного потенциала в лизате нейтрофилов периферической крови больных раком эндометрия и с миомой матки (группа сравнения) методом ИФА оценивали уровень воспалительных и ангиогенных цитокинов (VEGF-A, IL-17A, IL-1β, IL-6). В ядерной фракции нейтрофилов определяли экспрессию ядерного фактора NF-kB. В исследуемых группах оценивали отношение нейтрофилов к лимфоцитам (NLR). Статистическую обработку полученных данных проводили с использование ПО Statistica 10.

Установлено отсутствие значимых изменений NLR при раке эндометрия, по сравнению с контролем, и при миоме. Экспрессия NF-kB и VEGF были повышены по сравнению с контролем на всех изученных стадиях рака эндометрия и при миоме матки. Наблюдалась изменение уровня NF-kB в нейтрофилах в зависимости от дифференцировки опухоли. Между содержанием VEGF и NF-kB в нейтрофилах выявлена регрессионная взаимосвязь. Нами выявлено повышение уровня IL-1β и IL-6 в нейтрофилах при миоме матки и на разных стадиях рака эндометрия по сравнению с контролем. Уровень IL-1β был выше в нейтрофилах пациенток с умеренной и низкой дифференцировкой опухоли в сравнении с высокой.

IL-17A в лизате нейтрофилов был значимо снижен при миоме матки и на разных стадиях рака эндометрия по сравнению с контролем.

Отмечена умеренная обратная корреляционная связь между содержанием в нейтрофилах VEGF и IL-6 (r = -0,426; p = 0,001); заметная обратная связь между VEGF и IL-17А (r = -0,615; p < 0,001).

Комбинация показателей IL-6 и IL-17А в лизате нейтрофилов (по результатам мультивариантного анализа) может быть использована для дифференциальной диагностики рака эндометрия и миомы матки.

Таким образом, различия в экспрессии нейтрофилами воспалительных и ангиогенных цитокинов, входящих в NF-kB-зависиый сигналинг, свидетельствует о приобретении проопухолевых функций нейтрофилами при прогрессировании рака эндометрия. 

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. 

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The authors declare that there are no conflicts of interest present.