Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Nov 27

PMID 34830463

Citations 12

Authors

Viviana De Martino

Michela Rossi

Giulia Battafarano

Jessica Pepe

Salvatore Minisola

Andrea Del Fattore

Affiliations

Soon will be listed here.

Abstract

Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.

Citing Articles

Extracellular Vesicles from Highly Metastatic Osteosarcoma Cells Induce Pro-Tumorigenic Macrophage Phenotypes.

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Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations.

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Bone marrow mesenchymal stem cell-derived exosomes loaded with miR-26a through the novel immunomodulatory peptide DP7-C can promote osteogenesis.

Lai S, Deng L, Liu C, Li X, Fan L, Zhu Y Biotechnol Lett. 2023; 45(7):905-919.

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Role of cancer-associated mesenchymal stem cells in the tumor microenvironment: A review.

Wang K, Ding D Tzu Chi Med J. 2023; 35(1):24-30.

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Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment.

Tian H, Cao J, Li B, Nice E, Mao H, Zhang Y Bone Res. 2023; 11(1):11.

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References

Picci P . Osteosarcoma (osteogenic sarcoma). Orphanet J Rare Dis. 2007; 2:6. PMC: 1794406. DOI: 10.1186/1750-1172-2-6. View

Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A . The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004; 10(2):182-6. DOI: 10.1038/nm982. View

Zeng A, Yan W, Liu Y, Wang Z, Hu Q, Nie E . Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant phenotype and temozolomide chemoresistance in glioblastoma. Oncogene. 2017; 36(38):5369-5381. PMC: 5611480. DOI: 10.1038/onc.2017.134. View

Dumars C, Ngyuen J, Gaultier A, Lanel R, Corradini N, Gouin F . Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma. Oncotarget. 2016; 7(48):78343-78354. PMC: 5346643. DOI: 10.18632/oncotarget.13055. View

Perut F, Roncuzzi L, Zini N, Massa A, Baldini N . Extracellular Nanovesicles Secreted by Human Osteosarcoma Cells Promote Angiogenesis. Cancers (Basel). 2019; 11(6). PMC: 6627280. DOI: 10.3390/cancers11060779. View

Isakoff M, Bielack S, Meltzer P, Gorlick R . Osteosarcoma: Current Treatment and a Collaborative Pathway to Success. J Clin Oncol. 2015; 33(27):3029-35. PMC: 4979196. DOI: 10.1200/JCO.2014.59.4895. View

Phinney D, Di Giuseppe M, Njah J, Sala E, Shiva S, St Croix C . Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun. 2015; 6:8472. PMC: 4598952. DOI: 10.1038/ncomms9472. View

Bebelman M, Smit M, Pegtel D, Baglio S . Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther. 2018; 188:1-11. DOI: 10.1016/j.pharmthera.2018.02.013. View

Wang B, Xu M, Zheng K, Yu X . Effect of Unplanned Therapy on the Prognosis of Patients with Extremity Osteosarcoma. Sci Rep. 2016; 6:38783. PMC: 5143937. DOI: 10.1038/srep38783. View

10.

Rossi M, Battafarano G, DAgostini M, Del Fattore A . The Role of Extracellular Vesicles in Bone Metastasis. Int J Mol Sci. 2018; 19(4). PMC: 5979436. DOI: 10.3390/ijms19041136. View

11.

Zhang Y, Yang J, Zhao N, Wang C, Kamar S, Zhou Y . Progress in the chemotherapeutic treatment of osteosarcoma. Oncol Lett. 2018; 16(5):6228-6237. PMC: 6202490. DOI: 10.3892/ol.2018.9434. View

12.

Del Fattore A, Capannolo M, Rucci N . Bone and bone marrow: the same organ. Arch Biochem Biophys. 2010; 503(1):28-34. DOI: 10.1016/j.abb.2010.07.020. View

13.

Pullan J, Confeld M, Osborn J, Kim J, Sarkar K, Mallik S . Exosomes as Drug Carriers for Cancer Therapy. Mol Pharm. 2019; 16(5):1789-1798. DOI: 10.1021/acs.molpharmaceut.9b00104. View

14.

Macklin R, Wang H, Loo D, Martin S, Cumming A, Cai N . Extracellular vesicles secreted by highly metastatic clonal variants of osteosarcoma preferentially localize to the lungs and induce metastatic behaviour in poorly metastatic clones. Oncotarget. 2016; 7(28):43570-43587. PMC: 5190045. DOI: 10.18632/oncotarget.9781. View

15.

Cambier L, Stachelek K, Triska M, Jubran R, Huang M, Li W . Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers. Sci Rep. 2021; 11(1):94. PMC: 7794510. DOI: 10.1038/s41598-020-77398-z. View

16.

Nakamura K, Iwamoto R, Mekada E . Membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) and diphtheria toxin receptor-associated protein (DRAP27)/CD9 form a complex with integrin alpha 3 beta 1 at cell-cell contact sites. J Cell Biol. 1995; 129(6):1691-705. PMC: 2291180. DOI: 10.1083/jcb.129.6.1691. View

17.

Alfranca A, Martinez-Cruzado L, Tornin J, Abarrategi A, Amaral T, de Alava E . Bone microenvironment signals in osteosarcoma development. Cell Mol Life Sci. 2015; 72(16):3097-113. PMC: 11113487. DOI: 10.1007/s00018-015-1918-y. View

18.

Li Y, Lin S, Xie X, Zhu H, Fan T, Wang S . Highly enriched exosomal lncRNA OIP5-AS1 regulates osteosarcoma tumor angiogenesis and autophagy through miR-153 and ATG5. Am J Transl Res. 2021; 13(5):4211-4223. PMC: 8205742. View

19.

Laverdiere C, Hoang B, Yang R, Sowers R, Qin J, Meyers P . Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res. 2005; 11(7):2561-7. DOI: 10.1158/1078-0432.CCR-04-1089. View

20.

Klopp A, Gupta A, Spaeth E, Andreeff M, Marini 3rd F . Concise review: Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth?. Stem Cells. 2011; 29(1):11-9. PMC: 3059412. DOI: 10.1002/stem.559. View