tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2025-040tumors-1448Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL REPORTSОсобенности содержания VEGF-A, VEGF-С и их рецепторов в ткани опухоли и крови больных раком эндометрия в зависимости от гистологической структурыSpecifics of VEGF-A, VEGF-C and their receptors levels in the tumor and blood of patients with endometrial cancer depending on the histological typehttps://orcid.org/0000-0003-3618-6890ФранциянцЕ. М.FrantsiyantsE. M.

Франциянц Елена Михайловна

344037 Ростов-на-Дону, 14-я линия, 63

Frantsiyants Elena Mikhailovna

63 14 liniya St., Rostov-on-Don 344037

https://orcid.org/0000-0002-2302-8271БандовкинаВ. А.BandovkinaV. A.

Бандовкина Валерия Ахтямовна

344037 Ростов-на-Дону, 14-я линия, 63

Bandovkina Valeriya Akhtyamovna

63 14 liniya St., Rostov-on-Don 344037

https://orcid.org/0000-0002-4318-7587СуриковаЕ. И.SurikovaE. I.

Сурикова Екатерина Игоревна

344037 Ростов-на-Дону, 14-я линия, 63

Surikova Ekaterina Igorevna

63 14 liniya St., Rostov-on-Don 344037

https://orcid.org/0000-0002-7395-3086НескубинаИ. В.NeskubinaI. V.

Нескубина Ирина Валерьевна

344037 Ростов-на-Дону, 14-я линия, 63

Neskubina Irina Valerevna

63 14 liniya St., Rostov-on-Don 344037

neskubina.irina@mail.ruhttps://orcid.org/0000-0002-3711-8155ЧеряринаН. Д.CheryarinaN. D.

Черярина Наталья Дмитриевна

344037 Ростов-на-Дону, 14-я линия, 63

Cheryarina Natalya Dmitrievna

63 14 liniya St., Rostov-on-Don 344037

https://orcid.org/0000-0002-9683-2164МоисеенкоТ. И.MoiseenkoT.  I.

Моисеенко Татьяна Ивановна

344037 Ростов-на-Дону, 14-я линия, 63

Moiseenko Tatyana Ivanovna

63 14 liniya St., Rostov-on-Don 344037

https://orcid.org/0000-0002-7968-5078МеньшенинаА. П.MensheninaA. P.

Меньшенина Анна Петровна

344037 Ростов-на-Дону, 14-я линия, 63

Menshenina Anna Petrovna

63 14 liniya St., Rostov-on-Don 344037

https://orcid.org/0009-0003-7909-2883РогозинМ. А.RogozinM. A.

Рогозин Марк Андреевич

344037 Ростов-на-Дону, 14-я линия, 63

Rogozin Mark Andreevich

63 14 liniya St., Rostov-on-Don 344037

ФГБУ «Национальный медицинский исследовательский центр онкологии» Минздрава РоссииРоссияNational Medical Research Centre for OncologyRussian Federation20251504202515146–54Copyright © Франциянц Е.М., Бандовкина В.А., Сурикова Е.И., Нескубина И.В., Черярина Н.Д., Моисеенко Т.И., Меньшенина А.П., Рогозин М.А., 20252025Франциянц Е.М., Бандовкина В.А., Сурикова Е.И., Нескубина И.В., Черярина Н.Д., Моисеенко Т.И., Меньшенина А.П., Рогозин М.А.Frantsiyants E.M., Bandovkina V.A., Surikova E.I., Neskubina I.V., Cheryarina N.D., Moiseenko T.I., Menshenina A.P., Rogozin M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/1448Актуальность

Актуальность: Серозная (СРЭ) и светлоклеточная карциномы эндометрия (СвРЭ) являются редкими формами рака эндометрия (РЭ) и отличаются агрессивным течением.

Цель

Цель: Оценка различий в содержании факторов роста эндотелия сосудов (VEGF) и их растворимых рецепторов (sVEGF‑R) в ткани опухолей эндометрия и крови больных различными типами рака эндометрия.

Материалы и методы

Материалы и методы: Обследована 21 больная СвРЭ: 71,5 % с I–II стадией и 28,5 % с III–IV стадиями процесса, а также 20 больных СРЭ: 80 % — с I–II, 20 % — с III–IV стадиями. У всех была опухоль high grade G3. Группу контроля составили пациентки c эндометриоидной карциномой G3 (ЭР): 75 с I–II, 25 % — с III–IV стадиями. В качестве показателей нормы использовали данные в образцах интактного эндометрия, полученные от пациенток, прооперированных по поводу миомы матки (n = 20) и кровь условно здоровых женщин (n = 20). В 10 % гомогенатах образцов опухоли, интактного эндометрия и в образцах крови больных методом ИФА определяли уровень VEGF‑A, VEGF‑C, sVEGF‑R1, sVEGF‑R2. Статистическую обработку полученных результатов проводили с помощью программы Statistica 10.0.

Результаты

Результаты: Содержание VEGF‑A было выше в образцах опухоли в 1,8–2 раза по сравнению с интактным эндометрием, а в крови — в 3,8–12 раз выше по сравнению с показателями доноров. Содержание VEGF‑A в ткани эндометрия у онкологических больных не имело зависимости от гистоструктуры, в крови маркер был значимо выше у пациенток с редкими формами РЭ по сравнению с ЭР. Уровень sVEGF‑R1 в крови и опухоли превышал показатели нормы. Соотношение VEGF‑A / sVEGF‑R1 при ЭР не имело отличий от показателей нормы, тогда как у больных СвРЭ и СРЭ этот показатель в образцах опухоли снижался, а в крови повышался по сравнению с донорами. Содержание VEGF‑C в опухоли превышало показатели в интактном эндометрии у всех онкологических больных, но статистически значимо выше при СвРЭ и СРЭ по сравнению с ЭР. Концентрация sVEGF‑R2 при редких формах рака в опухоли была снижена. Уровень VEGF‑С в крови больных ЭР, СвРЭ и СРЭ был выше показателей здоровых доноров в 1,5–1,6 раза вне зависимости от гистологической структуры рака эндометрия, тогда как sVEGF‑R2 не имел достоверных отличий от здоровых доноров.

Заключение

Заключение: Выраженная активация sVEGF‑R1 и ингибирование sVEGF‑R2, обнаруженные при СвРЭ и СРЭ дает основание предполагать, что в опухоли при редких гистологических формах рака эндометрия, наряду с процессами ангиогенеза, имеет место васкулогенная мимикрия, вносящая свой вклад в агрессивность этих раков.

Background

Background: Serous endometrial carcinoma (SEC) and clear cell endometrial carcinoma (CCC) are rare forms of endometrial cancer (EC) characterized by an aggressive clinical course.

Purpose of the study

Purpose of the study: Evaluation of differences in the content of vascular endothelial growth factors (VEGF) and their soluble receptors (sVEGF-R) in endometrial tumor tissue and blood of patients with various types of EC.

Materials and methods

Materials and methods: The study included 21 patients with CCC (71.5 % with stage I–II, 28.5 % with stage III–IV), as well as 20 patients with SEC (80 % with stage I–II, 20 % with stage III–IV). All had high grade G3 tumors. The control group included patients with endometrioid endometrial carcinoma G3 (EEC): 75 with stage I–II, 25 % with stage III–IV. Samples of intact endometrium obtained from patients who underwent surgical procedures for uterine fibroids (n = 20) and blood samples from conditionally healthy women (n = 20) served as the normal parameters. The levels of VEGF-A, VEGF-C, sVEGF-R1, and sVEGF-R2 were determined by ELISA in 10 % of homogenates of tumor samples, intact endometrium, and blood samples. Statistical processing of the obtained results was performed using the Statistica 10.0 program.

Results

Results: The level of VEGF-A was found to be elevated in tumor samples by 1.8–2 times compared to intact endometrium, and in the blood by 3.8–12 times compared to donor values. The VEGF-A level in the endometrial tissue of cancer patients did not demonstrate a dependence on histology, while in the blood it exhibited a statistically significant increase in patients with rare forms of EC compared to EEC. The sVEGF-R1 levels in the blood and tumor samples were found to exceed standard values, with the highest levels observed in rare forms of EC. The VEGF-A / sVEGF-R1 ratio in EEC did not differ from the normal values, whereas in patients with CCC and SEC, the ratio decreased in tumor samples and increased in the blood compared to donors. The analysis further revealed that the concentration of VEGF-C in the tumor samples was higher than the values observed in the intact endometrium in all cancer patients. However, a statistically significant increase in the level of VEGF-C was observed in CCC and SEC compared to EEC. Conversely, the level of sVEGF-R2 in rare forms of cancer in the tumor was reduced. The level of VEGF-C in the blood of patients with EEC, CCC, and SEC was 1.5–1.6 times higher than that of healthy donors, regardless of the histological structure of endometrial cancer, while sVEGF-R2 did not have reliable differences from healthy donors.

Conclusion

Conclusion: The pronounced activation of sVEGF-R1 and inhibition of sVEGF-R2, as detected in CCC and SEC, suggests that in tumors of rare histological forms of endometrial cancer, along with angiogenesis processes, vasculogenic mimicry occurs, contributing to the aggressiveness of these cancers.

Рак эндометрияVEGF‑AVEGF‑CsVEGF‑R1sVEGF‑R2опухолькровьEndometrial cancerVEGF-AVEGF-CsVEGF-R1sVEGF-R2tumorbloodReferencesFadare O., Parkash V. Pathology of endometrioid and clear cell ovarian carcinoma. Surg Pathol Clin 2019;12(2):529–564. https://doi.org/10.1016/j.path.2019.01.009Fadare O., Parkash V. Pathology of endometrioid and clear cell ovarian carcinoma. Surg Pathol Clin 2019;12(2):529–564. https://doi.org/10.1016/j.path.2019.01.009Saarelainen S.K., Staff S., Peltonen N., et al. Endoglin, VEGF, and its receptors in predicting metastases in endometrial carcinoma. Tumour Biol 2014;35(5):4651–4657. https://doi.org/10.1007/s13277-014-1609-6Saarelainen S.K., Staff S., Peltonen N., et al. Endoglin, VEGF, and its receptors in predicting metastases in endometrial carcinoma. Tumour Biol 2014;35(5):4651–4657. https://doi.org/10.1007/s13277-014-1609-6Otto W., Macrae F., Serdzinski J., et al. Microsatellite instability and angiogenesis manifestations in stage IV sporadic colorectal carcinoma. Medicine (Baltimore) 2019;98(1):e13956. https://doi.org/10.1097/MD.0000000000013956Otto W., Macrae F., Serdzinski J., et al. Microsatellite instability and angiogenesis manifestations in stage IV sporadic colorectal carcinoma. Medicine (Baltimore) 2019;98(1):e13956. https://doi.org/10.1097/MD.0000000000013956Mahecha A.M., Wang H. The influence of vascular endothelial growth factor-A and matrix metalloproteinase-2 and -9 in angiogenesis, metastasis, and prognosis of endometrial cancer. Onco Targets Ther 2017;10:4617–4624. https://doi.org/10.2147/OTT.S132558Mahecha A.M., Wang H. The influence of vascular endothelial growth factor-A and matrix metalloproteinase-2 and -9 in angiogenesis, metastasis, and prognosis of endometrial cancer. Onco Targets Ther 2017;10:4617–4624. https://doi.org/10.2147/OTT.S132558Shito L., Semenza G.L. Hypoxia-inducible factors: master regulators of cancer progression. Trends Cancer 2016;2(12):758–770. https://doi.org/10.1016/j.trecan.2016.10.016Shito L., Semenza G.L. Hypoxia-inducible factors: master regulators of cancer progression. Trends Cancer 2016;2(12):758–770. https://doi.org/10.1016/j.trecan.2016.10.016De Smedt L., Lemahieu J., Palmans S., et al. Microsatellite instability versus stable colon carcinomas: analysis of tumor heterogeneity, inflammation and angiogenesis. Br J Cancer 2015;113(3):500–509. https://doi.org/10.1038/bjc.2015.213De Smedt L., Lemahieu J., Palmans S., et al. Microsatellite instability versus stable colon carcinomas: analysis of tumor heterogeneity, inflammation and angiogenesis. Br J Cancer 2015;113(3):500–509. https://doi.org/10.1038/bjc.2015.213Ramjiawan R.R., Griffioen A.W., Duda D.G. Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy? Angiogenesis 2017;20(2):185–204. https://doi.org/10.1007/s10456-017-9552-yRamjiawan R.R., Griffioen A.W., Duda D.G. Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy? Angiogenesis 2017;20(2):185–204. https://doi.org/10.1007/s10456-017-9552-yApte R.S., Chen D.S., Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell 2019;176(6):1248–1264. https://doi.org/10.1016/j.cell.2019.01.021Apte R.S., Chen D.S., Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell 2019;176(6):1248–1264. https://doi.org/10.1016/j.cell.2019.01.021Oplawski M., Dziobek K., Zmarzly N., et al. Expression profile of VEGF-C, VEGF-D and VEGFR-3 in different stages of endometrial cancer. Curr Pharm Biotechnol 2019;20(12):1004–1010. https://doi.org/10.2174/1389201020666190718164431Oplawski M., Dziobek K., Zmarzly N., et al. Expression profile of VEGF-C, VEGF-D and VEGFR-3 in different stages of endometrial cancer. Curr Pharm Biotechnol 2019;20(12):1004–1010. https://doi.org/10.2174/1389201020666190718164431Faria S.C., Devine K.E., Rao B., et al. Imaging and staging of endometrial cancer. Semin Ultrasound CT MR 2019;40(4):287–294. https://doi.org/10.1053/j.sult.2019.04.001Faria S.C., Devine K.E., Rao B., et al. Imaging and staging of endometrial cancer. Semin Ultrasound CT MR 2019;40(4):287–294. https://doi.org/10.1053/j.sult.2019.04.001Zhang G., Nie F., Zhao W., et al. Comparison of clinical characteristics and prognosis in endometrial carcinoma with different pathological types: a retrospective population-based study. World J Surg Oncol 2023;21(1):357. https://doi.org/10.1186/s12957-023-03241-0Zhang G., Nie F., Zhao W., et al. Comparison of clinical characteristics and prognosis in endometrial carcinoma with different pathological types: a retrospective population-based study. World J Surg Oncol 2023;21(1):357. https://doi.org/10.1186/s12957-023-03241-0Ferrara N. Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell 2010;21(5):687–690. https://doi.org/10.1091/mbc.e09-07-0590Ferrara N. Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell 2010;21(5):687–690. https://doi.org/10.1091/mbc.e09-07-0590Ferrara N., Adamis A.P. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov 2016;15(6):385–403. https://doi.org/10.1038/nrd.2015.17Ferrara N., Adamis A.P. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov 2016;15(6):385–403. https://doi.org/10.1038/nrd.2015.17Harris H.J., Łaniewski P., Cui H., et al. Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer. Mol Biomed 2024;5(1):55. https://doi.org/10.1186/s43556-024-00219-6Harris H.J., Łaniewski P., Cui H., et al. Cervicovaginal lavages uncover growth factors as key biomarkers for early diagnosis and prognosis of endometrial cancer. Mol Biomed 2024;5(1):55. https://doi.org/10.1186/s43556-024-00219-6Cai S., Zhang Y.X., Han K., Ding Y.Q. Expressions and clinical significance of COX-2, VEGF-C, and EFGR in endometrial carcinoma. Arch Gynecol Obstet 2017;296(1):93–98. https://doi.org/10.1007/s00404-017-4386-9Cai S., Zhang Y.X., Han K., Ding Y.Q. Expressions and clinical significance of COX-2, VEGF-C, and EFGR in endometrial carcinoma. Arch Gynecol Obstet 2017;296(1):93–98. https://doi.org/10.1007/s00404-017-4386-9Li C., Yu J., Fu Z. Application of CT and MRI combined with VEGF-C and EGFR for staging of endometrial cancer. Am J Transl Res 2021;13(6):7164–7171Li C., Yu J., Fu Z. Application of CT and MRI combined with VEGF-C and EGFR for staging of endometrial cancer. Am J Transl Res 2021;13(6):7164–7171Motwani J., Eccles M.R. Genetic and genomic mechanisms of melanoma development, invasion and metastasis. Genes (Basel) 2021;12(10):1543. https://doi.org/10.3390/genes12101543Motwani J., Eccles M.R. Genetic and genomic mechanisms of melanoma development, invasion and metastasis. Genes (Basel) 2021;12(10):1543. https://doi.org/10.3390/genes12101543Льянова А.А., Владимирова Л.Ю., Ульянова Е.П. и соавт. Динамика изменения экспрессии фактора неоангиогенеза VEGF в биоптатах опухолевой ткани у больных плоскоклеточным раком слизистой оболочки полости рта при проведении терапии цетуксимабом и химиотерапии. Южно-Российский онкологический журнал 2022;3(4):40–48.Lyanova A.A., Vladimirova L.Yu., Ulyanova E.P., et al. Dynamics of changes in the expression of neoangiogenesis factor VEGF in tumor tissue biopsies in patients with squamous cell carcinoma of the oral mucosa during cetuximab therapy and chemotherapy. South Russian Journal of Cancer 2022;3(4):40–48 (In Russ.). https://doi.org/10.37748/2686-9039-2022-3-4-4Peach C.J., Mignone V.W., Arruda M.A., et al. Molecular pharmacology of VEGF-A isoforms: binding and signalling at VEGFR2. Int J Mol Sci 2018;19(4):1264. https://doi.org/10.3390/ijms19041264Peach C.J., Mignone V.W., Arruda M.A., et al. Molecular pharmacology of VEGF-A isoforms: binding and signalling at VEGFR2. Int J Mol Sci 2018;19(4):1264. https://doi.org/10.3390/ijms19041264Koch S., Klasson-Welsh L. Vascular endothelial growth factor receptor signaling. Cold Spring Harb Perspect Med 2012;2(7):a006502. https://doi.org/10.1101/cshperspect.a006502Koch S., Klasson-Welsh L. Vascular endothelial growth factor receptor signaling. Cold Spring Harb Perspect Med 2012;2(7):a006502. https://doi.org/10.1101/cshperspect.a006502Yao J., Wu S., Zhuang G., et al. Expression of functional VEGFR-1 receptor in tumor cells is a major determinant of the efficacy of anti-PlGF antibodies. Proc Natl Acad Sci USA 2011;108(28):11590–11595. https://doi.org/10.1073/pnas.1109029108Yao J., Wu S., Zhuang G., et al. Expression of functional VEGFR-1 receptor in tumor cells is a major determinant of the efficacy of anti-PlGF antibodies. Proc Natl Acad Sci USA 2011;108(28):11590–11595. https://doi.org/10.1073/pnas.1109029108Kaplan R.N., Riba R.D., Zacharoulis S., et al. VEGFR1-positive bone marrow hematopoietic progenitor cells initiate a premetastatic niche. Nature 2005;438(7069):820–827. https://doi.org/10.1038/nature04186Kaplan R.N., Riba R.D., Zacharoulis S., et al. VEGFR1-positive bone marrow hematopoietic progenitor cells initiate a premetastatic niche. Nature 2005;438(7069):820–827. https://doi.org/10.1038/nature04186Кит О.И., Котиева И.М., Франциянц Е.М. и др. Регуляция ангиогенеза факторами роста в интактной и патологически измененной коже самок мышей при злокачественной меланоме, развивающейся на фоне хронической боли. Российский журнал боли 2017;54(3–4):17–25.Kit O.I., Kotieva I.M., Franzyants E.M., et al. Regulation of angiogenesis by growth factors in intact and pathologically altered skin of female mice with malignant melanoma developing on the background of chronic pain. The Russian Journal of Pain 2017;54(3–4):17–25 (In Russ.)Mao J.M., Liu J., Guo G., et al. Vasculogenic mimicry of glioblastoma: signaling pathways and potential targets for antiangiogenic therapy. Biomark Res 2015;3:8. https://doi.org/10.1186/s40364-015-0034-3Mao J.M., Liu J., Guo G., et al. Vasculogenic mimicry of glioblastoma: signaling pathways and potential targets for antiangiogenic therapy. Biomark Res 2015;3:8. https://doi.org/10.1186/s40364-015-0034-3Donnem T., Hu J., Ferguson M., et al. Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment? Cancer Med 2013;2(4):427–436. https://doi.org/10.1002/cam4.105Donnem T., Hu J., Ferguson M., et al. Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment? Cancer Med 2013;2(4):427–436. https://doi.org/10.1002/cam4.105Yu Z., Zhang Q., Wei S., et al. CD146 + CAFs promote progression of endometrial cancer by inducing angiogenesis and vasculogenic mimicry via IL-10/JAK1/STAT3 pathway. Cell Commun Signal 2024;22(1):170. https://doi.org/10.1186/s12964-024-01550-9Yu Z., Zhang Q., Wei S., et al. CD146 + CAFs promote progression of endometrial cancer by inducing angiogenesis and vasculogenic mimicry via IL-10/JAK1/STAT3 pathway. Cell Commun Signal 2024;22(1):170. https://doi.org/10.1186/s12964-024-01550-9Frank N.Y., Sсhatton T., Kim S., et al. VEGFR-1 expressed by malignant melanoma-initiating cells is required for tumor growth. Cancer Res 2011;71(4):1474–1485. https://doi.org/10.1158/0008-5472.CAN-10-1660Frank N.Y., Sсhatton T., Kim S., et al. VEGFR-1 expressed by malignant melanoma-initiating cells is required for tumor growth. Cancer Res 2011;71(4):1474–1485. https://doi.org/10.1158/0008-5472.CAN-10-1660Shen Y., Quan Q., Wang M., et al. Tumor vasculogenic mimicry formation as an unfavorable prognostic indicator in patients with breast cancer. Oncotarget 2017;8(34):56408–56416. https://doi.org/10.18632/oncotarget.16919Shen Y., Quan Q., Wang M., et al. Tumor vasculogenic mimicry formation as an unfavorable prognostic indicator in patients with breast cancer. Oncotarget 2017;8(34):56408–56416. https://doi.org/10.18632/oncotarget.16919Delgado-Bellido D., Serrano-Saenz S., Fernández-Cortés M., Oliver F.J. Vasculogenic mimicry signaling revisited: focus on non-vascular VE-cadherin. Mol Cancer 2017;16(1):65. https://doi.org/10.1186/s12943-017-0631-xDelgado-Bellido D., Serrano-Saenz S., Fernández-Cortés M., Oliver F.J. Vasculogenic mimicry signaling revisited: focus on non-vascular VE-cadherin. Mol Cancer 2017;16(1):65. https://doi.org/10.1186/s12943-017-0631-xSaravanan S., Vimalraj S., Pavani K., et al. Intussusceptional angiogenesis as a key therapeutic target for cancer treatment. Life Sci 2020;252:117670. https://doi.org/10.1016/j.lfs.2020.117670Saravanan S., Vimalraj S., Pavani K., et al. Intussusceptional angiogenesis as a key therapeutic target for cancer treatment. Life Sci 2020;252:117670. https://doi.org/10.1016/j.lfs.2020.117670Mabeta P., Steenkamp V. The VEGF/VEGFR axisrevisited: implications for cancertherapy. Int J Mol Sci 2022;23(24):15585. https://doi.org/10.3390/ijms232415585Mabeta P., Steenkamp V. The VEGF/VEGFR axisrevisited: implications for cancertherapy. Int J Mol Sci 2022;23(24):15585. https://doi.org/10.3390/ijms232415585Seftor R.E., Hess A.R., Seftor E.A., et al. Tumor cell vasculogenic mimicry: from controversies to therapeutic promise. Am J Pathol 2012;181(4):1115–1125. https://doi.org/10.1016/j.ajpath.2012.07.013Seftor R.E., Hess A.R., Seftor E.A., et al. Tumor cell vasculogenic mimicry: from controversies to therapeutic promise. Am J Pathol 2012;181(4):1115–1125. https://doi.org/10.1016/j.ajpath.2012.07.013Вартанян А.А. Альтернативное кровоснабжение в костном мозге при онкогематологических заболеваниях. Клиническая онкогематология 2014;7(4):491–500.Vartanyan A.A. Supplemental blood circulation system in hematologic malignancies. Clin. Oncohematol 2014;7(4):491–500 (In Russ.)

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