Blood exosomes of patients with malignant neoplasms of bones and articular cartilage: connection with tumor progression and practical value in clinical medicine

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Relevance. Primary malignant neoplasms of bones and articular cartilage account for about 0.2% of all cancer cases and are characterized by an aggressive course, high tendency to metastasize, and resistance to therapy, which leads to unsatisfactory survival rates, especially at late stages. Existing diagnostic methods (visualization, biopsy) are associated with risks and have limitations, including the lack of specific immunohistochemical markers and insufficient sensitivity for early detection of these diseases.

Objective. A review of the literature to assess the use of “liquid biopsy” based on blood exosomes for the diagnosis and monitoring of malignant neoplasms of bones and articular cartilage.

Material and methods. The work used data from 46 articles devoted to the study of the composition and functions of exosomes, their role in the oncogenesis of malignant neoplasms of bones and articular cartilage, as well as the results of studies on the use of the molecular cargo of exosomes as a source of potential biomarkers.

Results. It has been established that miR-25-3p has a high diagnostic potential for diagnosing osteosarcoma, miR-525 for chondrosarcoma, and miR-152 and miR-34a for Ewing’s sarcoma, which are involved in regulating the proliferative activity of tumor cells. Thus, analysis of exosome contents allows us to determine the tumor type, predict the response to therapy and the risk of metastasis, overcoming the limitations of traditional biopsy.

About the authors

Oleg E. Olgin

E.N. Meshalkin National Research Medical Center of the Ministry of Health of the Russian Federation; Institute of Medicine and Medical Technologies of Novosibirsk State University

Email: o.olgin@g.nsu.ru

Laboratory Assistant, Oncology and Radiotherapy Research Department of the Institute of Oncology and Neurosurgery; 6th Year Student

Russian Federation, Rechkunovskaya str., 15, Novosibirsk, 630055; Pirogova str., 1, Novosibirsk, 630090

Aleksandr A. Zheravin

E.N. Meshalkin National Research Medical Center of the Ministry of Health of the Russian Federation

Email: zheravin2010@yandex.ru
ORCID iD: 0000-0003-3047-4613

Candidate of Medical Sciences, Leading Researcher, Oncology and Radiotherapy Research Department at the Institute of Oncology and Neurosurgery

Russian Federation, Rechkunovskaya str., 15, Novosibirsk, 630055

Mamed D. Aliev

Federal State Budgetary Institution “National Medical Research Center of Radiology” of the Ministry of Health of the Russian Federation

Email: oncology@inbox.ru
ORCID iD: 0000-0003-2706-4138

Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Advisor of the General Director

Russian Federation, 2nd Botkinsky Lane, 3, Moscow, 125284

Yevgeny L. Choynzonov

Tomsk National Research Medical Center

Email: choynzonov@gmail.com
ORCID iD: 0000-0002-3651-0665

Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Director of the Сancer Research Institute

Russian Federation, Kooperativny Str., 5, Tomsk, 634009

Alena L. Chernyshova

E.N. Meshalkin National Research Medical Center of the Ministry of Health of the Russian Federation; Institute of Medicine and Medical Technologies of Novosibirsk State University

Email: alacher@list.ru
ORCID iD: 0000-0002-8194-2811

Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Director of the Institute of Oncology and Neurosurgery; Associate Professor of the Department of Surgical Disease

Russian Federation, Rechkunovskaya str., 15, Novosibirsk, 630055; Pirogova str., 1, Novosibirsk, 630090

Svetlana N. Tamkovich

E.N. Meshalkin National Research Medical Center of the Ministry of Health of the Russian Federation; Institute of Medicine and Medical Technologies of Novosibirsk State University; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: tamkovich_sn@meshalkin.ru
ORCID iD: 0000-0001-7774-943X

Candidate of Biological Sciences, Associate Professor, Head of the Oncology and Radiotherapy Research Department, Institute of Oncology and Neurosurgery; Associate Professor of the Department of Clinical Biochemistry; Senior Researcher of Laboratory of Invasive Medical Technology

Russian Federation, Rechkunovskaya str., 15, Novosibirsk, 630055; Pirogova str., 1, Novosibirsk, 630090; Lavrentiev Ave., 8, Novosibirsk, 630090

References

  1. Ассоциация онкологов России Восточно-европейская группа по изучению сарком Российское общество клинической онкологии. Клинические рекомендации “Саркомы костей” (письмо Министерства здравоохранения Российской Федерации от 22.07.2022). М., 2022; 71. [Association of Oncologists of Russia Eastern European Sarcoma Research Group Russian Society of Clinical Oncology. Clinical recommendations of “Bone Sarcoma» (letter from the Ministry of Health of the Russian Federation dated 07/22/2022). Moscow, 2022; 71 (in Russian)].
  2. Каприна А.Д. и др. Злокачественные новообразования в России в 2023 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2024; 276. [Kaprin A.D. et al. Malignant neoplasms in Russia in 2023 (morbidity and mortality). Moscow: P.A. Herzen Moscow Institute of Medical Sciences – branch of the Federal State Budgetary Institution «NMITS of Radiology» of the Ministry of Health of Russia, 2024; 276 (in Russian)].
  3. Валиев А.К., Тарарыкова А.А., Тепляков В.В., Мусаев Э.Р., Рогожин Д.В., Сушенцов Е.А., Мачак Г.Н. и др. Злокачественные опухоли костей. Злокачественные опухоли. 2023; 3s2-1. [Valiev A.K., Tararykova A.A., Teplyakov V.V., Musaev E.R., Rogozhin D.V., Sushentsov E.A., Machak G.N. et al. Malignant bone tumors. Malignant tumors. 2023; №3s2-1 (in Russian)].
  4. Фритц Э., Перси К., Джек Э., Шанмугаратнам К., Собин Л., Паркин Д.М., Уилан Ш. Международная классификация болезней – онкология (МКБ-О), 3 издание, 1 пересмотр. Пер. с англ. А.В. Филочкиной, под ред. А.М. Беляева, О.Ф. Чепика, А.С. Артемьевой, А.А. Барчука, Ю.И. Комарова. СПб.: Издательство «Вопросы онкологии», 2017; 52–4. [Fritz E., Percy K., Jack E., Shanmugaratnam K., Sobin L., Parkin D.M., Whelan S. International Classification of Diseases – Oncology (ICD-O), 3rd edition, 1st revision. Translated from English by A.V. Filochkina, edited by A.M. Belyaev, O.F. Chepik, A.S. Artemyeva, A.A. Barchuk, Yu.I. Komarova. St. Petersburg: Publishing House «Questions of Oncology», 2017; 52–4 (in Russian)].
  5. Пономарев В., Чернышева О., Поликарпова С., Богуш Е., Высоцкая И., Кирсанов В., Тупицын. Детекция циркулирующих опухолевых клеток у больных раком молочной железы I–III стадий. Патология кровообращения и кардиохирургия. 2020; 24 (3): 107–11. https://doi.org/10.21688/1681-3472-2020-3-107-111 [Ponomarev V., Chernysheva O., Polikarpova S., Bogush E., Vysotskaya I., Kirsanov V., Tupitsyn. Detection of circulating tumor cells in patients with breast cancer stages I–III . Pathology of blood circulation and cardiac surgery. 2020; 24 (3): 107–11. https://doi.org/10.21688/1681-3472-2020-3-107-111 (in Russian)].
  6. Феденко А.А., Бохян А.Ю., Горбунова В.А., Махсон А.Н., Тепляков В.В. Практические рекомендации по лечению первичных злокачественных опухолей костей (остеосаркомы, саркомы Юинга) рекомендации восточно-европейской группы по изучению сарком. Злокачественные опухоли. 2021; 3S2-1. [Fedenko A.A., Bokhyan A.Yu., Gorbunova V.A., Makhson A.N., Teplyakov V.V. Practical recommendations for the treatment of primary malignant bone tumors (osteosarcomas, Ewing’s sarcoma) recommendations of the Eastern European sarcoma study group. Malignant tumors. 2021; 3S2-1 (in Russian)].
  7. Шалыга И.Ф., Ачинович С.Л., Козловская Т.В., Мартемьянова Л.А., Турченко С.Ю., Авижец Ю.Н. Саркома Юинга. Проблемы здоровья и экологии. 2018; 1 (55): 101–5. [Shalyga I.F., Achinovich S.L., Kozlovskaya T.V., Martemyanova L.A., Turchenko S.Yu., Avizhets Yu.N. Ewing’s sarcoma. Problems of health and ecology. 2018; 1 (55): 101–5 (in Russian)].
  8. Самбурова Н.В., Пименов И.А., Жевак Т.Н., Литвицкий П.Ф. Саркома Юинга: молекулярногенетические механизмы патогенеза ВСП. 2019; 4: 257–63. [Samburova N.V., Pimenov I.A., Zhevak T.N., Litvitsky P.F. Ewing’s sarcoma: molecular genetic mechanisms of pathogenesis VSP. 2019; 4: 257–63 (in Russian)].
  9. Джугашвили Е.И., Юнусова Н.В., Яловая А.И., Григорьева А.Е., Середа Е.Е., Коломиец Л.А., Тамкович С.Н. Сравнительная оценка уровней опухолеассоциированных миркоРНК экзосом плазмы крови и асцитической жидкости пациентов с раком яичников. Успехи молекулярной онкологии. 2023; 2: 108–16. [Dzhugashvili E.I., Yunusova N.V., Yalovaya A.I., Grigorieva A.E., Sereda E.E., Kolomiets L.A., Tamkovich S.N. Comparative assessment of levels of tumor-associated miRNAs in exosomes of blood plasma and ascitic fluid of patients with ovarian cancer. Advances in Molecular Oncology. 2023; 2: 108–16 (in Russian)].
  10. Самойлова Е.М., Кальсин В.А., Беспалова В.А., Девиченский В.М., Баклаушев В.П. Экзосомы: от биологии к клинике. Гены и клетки. 2017; 4: 7–19. [Samoylova E.M., Kalsin V.A., Bespalova V.A., Devichensky V.M., Baklaushev V.P. Exosomes: from biology to clinic. Genes and cells. 2017; 4: 7–19 (in Russian)].
  11. Тихонова М.В., Карачунский А.И., Поспелов В.И., Румянцев С.А., Румянцев А.Г. Перспективы использования экзосом опухолевых клеток в диагностике, мониторинге и терапии злокачественных заболеваний. РЖДГиО. 2017; 2: 40–5. [Tikhonova M.V., Karachunsky A.I., Pospelov V.I., Rumyantsev S.A., Rumyantsev A.G. Prospects for the use of tumor cell exosomes in diagnostics, monitoring and therapy of malignant diseases. Russian J. of Pediatric Hematology and Oncology. 2017; 2: 40–5 (in Russian)].
  12. Шефер А.А., Фрик Я.А., Тамкович С.Н. Диагностический и терапевтический потенциал белков экзосом при раке молочной железы. Успехи молекулярной онкологии. 2023; 2: 58–69. [Shefer A.A., Frick Ya.A., Tamkovich S.N. Diagnostic and therapeutic potential of exosome proteins in breast cancer. Advances in Molecular Oncology. 2023; 2: 58–69 (in Russian)].
  13. Ventura S., Aryee D.N.T., Felicetti F., De Feo A., Mancarella C., Manara M.C., Picci P. et al. CD99 regulates neural differentiation of Ewing sarcoma cells through miR-34a-Notch-mediated control of NF-κB signaling. Oncogene. 2016; 3944–54. doi: 10.1038/onc.2015.463.
  14. Boehme K.A., Schleicher S.B., Traub F., Rolauffs B. Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance. Int. J. Mol. Sci. 2018; 311. doi: 10.3390/ijms19010311.
  15. Chicón-Bosch M., Tirado O.M. Exosomes in Bone Sarcomas: Key Players in Metastasis. Cells. 2020; 241. doi: 10.3390/cells9010241.
  16. Zając A., Kopeć S., Szostakowski B., Spałek M., Fiedorowicz M., Bylina E., Filipowicz P. et al. Chondrosarcoma-from Molecular Pathology to Novel Therapies. Cancers. 2021; 2390. doi: 10.3390/cancers13102390.
  17. Fujiwara T., Uotani K., Yoshida A., Morita T., Nezu Y., Kobayashi E., Yoshida A. et al. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma. Oncotarget. 2017; 33375–92. doi: 10.18632/oncotarget.16498.
  18. Wang J.W., Wu X.F., Gu X.J., Jiang X.H. Exosomal miR-1228 from cancer-associated fibroblasts promotes cell migration and invasion of osteosarcoma by directly targeting SC. Oncol. Res. 2019; 979–86. doi: 10.3727/096504018X15336368805108.
  19. Gong L., Bao Q., Hu C., Wang J., Zhou Q., Wei L., Tong L. et al. Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1. Biochem. Biophys. Res. Commun. 2018; 170–6. doi: 10.1016/j.bbrc.2018.04.016.
  20. Yang F., Ning Z., Ma L., Liu W., Shao C., Shu Y., Shen H. Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts. Mol Cancer. 2017; 148. doi: 10.1186/s12943-017-0718-4.
  21. Khanicheragh P., Abbasi-Malati Z., Saghebasl S., Hassanpour P., Milani S.Z., Rahbarghazi R., Hasani A. Exosomes and breast cancer angiogenesis; Highlights in intercellular communication. Cancer Cell Int. 2024; 402. doi: 10.1186/s12935-024-03606-9.
  22. Fu H., Wu Y., Chen J., Hu X., Wang X., Xu G. Exosomes and osteosarcoma drug resistance. Front Oncol. 2023; 13: 1133726. doi: 10.3389/fonc.2023.1133726.
  23. Yu D., Li Y., Wang M., Gu J., Xu W., Cai H., Fang X. et al. Exosomes as a new frontier of cancer liquid biopsy. Mol Cancer. 2022; 21. doi: 10.1186/s12943-022-01509-9.
  24. De Feo A., Sciandra M., Ferracin M., Felicetti F., Astolfi A., Pignochino Y., Picci P. et al. Exosomes from CD99-deprived Ewing sarcoma cells reverse tumor malignancy by inhibiting cell migration and promoting neural differentiation. Cell Death Dis. 2019; 1–15. doi: 10.1038/s41419-019-1675-1.
  25. Zhang X.B., Zhang R.H., Su X., Qi J., Hu Y.C., Shi J.T., Zhang K. et al. Exosomes in osteosarcoma research and preclinical practice. Am J Transl Res. 2021; 882–97.
  26. Tenchov R., Sasso J.M., Wang X., Liaw W.S., Chen C.A., Zhou Q.A. Exosomes–Nature’s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics. ACS Nano. 2022; 17802–46. doi: 10.1021/acsnano.2c08774.
  27. Ferguson J.L., Turner S.P. Bone Cancer: Diagnosis and Treatment Principles. Am Fam Physician. 2018; 205–13.
  28. Fujiwara T., Ozaki T. Overcoming Therapeutic Resistance of Bone Sarcomas: Overview of the Molecular Mechanisms and Therapeutic Targets for Bone Sarcoma Stem. Cells. Stem Cells Int. 2016; 1–13. doi: 10.1155/2016/2603092.
  29. Lee Y.J., Shin K.J., Jang H.J., Ryu J.S., Lee C.Y., Yoon J.H., Seo J.K. et al. GPR143 controls ESCRT-dependent exosome biogenesis and promotes cancer metastasis. Dev Cell. 2023; 320–34. doi: 10.1016/j.devcel.2023.01.006.
  30. Krylova S.V., Feng D. The Machinery of Exosomes: Biogenesis, Release, and Uptake. Int. J. Mol. Sci. 2023; 1337. doi: 10.3390/ijms24021337
  31. Joshi G.K., Deitz-McElyea S., Liyanage T., Lawrence K., Mali S., Sardar R., Korc M. Label-Free Nanoplasmonic-Based Short Noncoding RNA Sensing at Attomolar Concentrations Allows for Quantitative and Highly Specific Assay of MicroRNA-10b in Biological Fluids and Circulating Exosomes. ACS Nano. 2015; 11075–89. doi: 10.1021/acsnano.5b04527.
  32. Georgeanu V.A., Mămuleanu M., Ghiea S., Selișteanu, D. Malignant Bone Tumors Diagnosis Using Magnetic Resonance Imaging Based on Deep Learning Algorithms. Medicina 2022; 58: 636. doi: 10.3390/medicina58050636.
  33. Liu B., Song X., Yan Z., Yang H., Shi Y., Wu J. MicroRNA-525 enhances chondrosarcoma malignancy by targeting F-spondin 1. Oncol Lett. 2019; 781–8. doi: 10.3892/ol.2018.9711.
  34. Chen J.C., Shih H.C., Lin C.Y., Guo J.H., Huang C., Huang H.C., Chong Z.Y. et al. MicroRNA-631 Resensitizes Doxorubicin-Resistant Chondrosarcoma Cells by Targeting Apelin. Int. J. Mol. Sci. 2023; 24 (1): 839. doi: 10.3390/ijms24010839.
  35. Zhang P., Li J., Song Y., Wang X. MiR-129-5p inhibits proliferation and invasion of chondrosarcoma cells by regulating SOX4/Wnt/β-catenin signaling pathway. Cell. Physiol. Biochem. 2017; 242–53. doi: 10.33594/000000608.
  36. Ma D., Huang C., Zheng J., Tang J., Li J., Yang J., Yang R. Quantitative detection of exosomal microRNA extracted from human blood based on surface-enhanced Raman scattering. Biosens Bioelectron. 2018; 167–73. doi: 10.1016/j.bios.2017.08.062.
  37. Rajani R., Gibbs C.P. Treatment of Bone Tumors. Surg. Pathol. Clin. 2012; 301–18. doi: 10.1016/j.path.2011.07.015.
  38. Bădilă A.E., Rădulescu D.M., Niculescu A.-G., Grumezescu A.M., Rădulescu M., Rădulescu A.R. Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review. Cancers. 2021; 4229. doi: 10.3390/cancers13164229
  39. Wu H., Zheng S., He Q., Li Y. Recent Advances of Circular RNAs as Biomarkers for Osteosarcoma. Int. J. Gen Med. 2023; 173–83. doi: 10.2147/IJGM.S380834.
  40. Jafarzadeh A., Naseri B., Khorramdelazad H., Jafarzadeh S., Ghorbaninezhad F., Asgari Z., Masoumi J. et al. Reciprocal Interactions Between Apelin and Noncoding RNAs in Cancer Progression. Cell Biochem Funct. 2024; e4116. doi: 10.1002/cbf.4116.
  41. Siegel R.L., Mph K.D.M., Jemal A. Cancer statistics. CA A Cancer J. Clin. 2020; 7–30. doi: 10.3322/caac.21590.
  42. Taran R., Taran S., Malipatil N. Pediatric osteosarcoma: An updated review. Indian J. Med Paediatr. Oncol. 2017; 33–43. doi: 10.4103/0971-5851.203513.
  43. Tzeng H.-E., Lin S.-L., Thadevoos L.-A., Ko C.-Y., Liu J.-F., Huang Y.-W., Lin et al. The mir-423-5p/MMP-2 Axis Regulates the Nerve Growth Factor-Induced Promotion of Chondrosarcoma Metastasis. Cancers. 2021; 3347. doi: 10.3390/cancers13133347.
  44. Tzanakakis G., Giatagana E.-M., Berdiaki A., Spyridaki I., Hida K., Neagu M., Tsatsakis A. et al. The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis. Cancers. 2021; 2478. doi: 10.3390/cancers13102478.
  45. Kawano M., Tanaka K., Itonaga I., Iwasaki T., Kubota Y., Tsumura H. Tumor-suppressive microRNA-152 inhibits the proliferation of Ewing’s sarcoma cells by targeting CDK5R1. Sci Rep. 2023; 18546. doi: 10.1038/s41598-023-45833-6.
  46. Weinschenk R.C., Wang W.L., Lewis V.O. Chondrosarcoma. J. Am. Acad Orthop Surg. 2021; 553–62. doi: 10.5435/JAAOS-D-20-01188.
  47. Zhang L., Yu D. Exosomes in cancer development, metastasis, and immunity. Biochim Biophys Acta Rev. Cancer. 2019; 455–68. doi: 10.1016/j.bbcan.2019.04.004.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).