Research progress of exosomes in osteosarcoma_West China Medical Journal

Authors：

CHENG Jie ¹ , SUN Yi ² , DING Yinliang ² ,  WANG Wenji ³ , ZHAO Haiyan ³ , ZHANG Fanyun ⁴

1. Department of Orthopedics, First People’s Hospital of Tianshui, Tianshui, Gansu 741000, P. R. China;
2. The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu 730000, P. R. China;
3. Department of Orthopedics, the First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;
4. Department of Orthopedics, Linxia County People’s Hospital, Linxia, Gansu 731800, P. R. China;

Corresponding author：

WANG Wenji, Email: ldyyjzwwj@163.com

Keywords：

Exosomes; osteosarcoma; RNA; therapy

DOI：

10.7507/1002-0179.202212139

Video：

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Abstract Full text Figures/Tables Video References Cited by

Exosomes are a type of tiny vesicles released by cells, which contain bioactive molecules such as proteins, nucleic acids, and lipids secreted by cells. Exosomes released by different cells play an important role in tumor development and metastasis. These exosomes can regulate the tumor microenvironment, promote the tumor growth and invasion, and participate in the process of distant metastasis by carrying specific proteins and nucleic acids. In addition, some biomarkers in exosomes can serve as potential biomarkers for early diagnosis and prognosis evaluation of osteosarcoma. This article reviews the research progress of exosomes in osteosarcoma, aiming to gain a deeper understanding of their mechanisms of action in this disease and provide a reference for the development of new treatment strategies and prognostic evaluation indicators.

Citation： CHENG Jie, SUN Yi, DING Yinliang, WANG Wenji, ZHAO Haiyan, ZHANG Fanyun. Research progress of exosomes in osteosarcoma. West China Medical Journal, 2023, 38(6): 924-929. doi: 10.7507/1002-0179.202212139 Copy

1.	Gurunathan S, Kang MH, Kim JH. A comprehensive review on factors influences biogenesis, functions, therapeutic and clinical implications of exosomes. Int J Nanomedicine, 2021, 16: 1281-1312.
2.	Gill J, Gorlick R. Advancing therapy for osteosarcoma. Nat Rev Clin Oncol, 2021, 18(10): 609-624.
3.	Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478): eaau6977.
4.	Li C, Teixeira AF, Zhu HJ, et al. Cancer associated-fibroblast-derived exosomes in cancer progression. Mol Cancer, 2021, 20(1): 154.
5.	Murillo OD, Thistlethwaite W, Rozowsky J, et al. exRNA atlas analysis reveals distinct extracellular RNA cargo types and their carriers present across human biofluids. Cell, 2019, 177(2): 463-477.e15.
6.	Tang XH, Guo T, Gao XY, et al. Exosome-derived noncoding RNAs in gastric cancer: functions and clinical applications. Mol Cancer, 2021, 20(1): 99.
7.	Yang J, Hu Y, Wang L, et al. Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating notch signaling pathway. Bioengineered, 2021, 12(2): 11007-11017.
8.	Kersten K, Hu KH, Combes AJ, et al. Spatiotemporal co-dependency between macrophages and exhausted CD8⁺ T cells in cancer. Cancer Cell, 2022, 40(6): 624-638.e9.
9.	Zhang H, Yu Y, Wang J, et al. Macrophages-derived exosomal lncRNA LIFR-AS1 promotes osteosarcoma cell progression via miR-29a/NFIA axis. Cancer Cell Int, 2021, 21(1): 192.
10.	Cersosimo F, Lonardi S, Bernardini G, et al. Tumor-associated macrophages in osteosarcoma: from mechanisms to therapy. Int J Mol Sci, 2020, 21(15): 5207.
11.	Liu W, Long Q, Zhang W, et al. miRNA-221-3p derived from M2-polarized tumor-associated macrophage exosomes aggravates the growth and metastasis of osteosarcoma through SOCS3/JAK2/STAT3 axis. Aging (Albany NY), 2021, 13(15): 19760-19775.
12.	Ye Z, Zheng Z, Peng L. MicroRNA profiling of serum exosomes in patients with osteosarcoma by high-throughput sequencing. J Investig Med, 2020, 68(4): 893-901.
13.	Wang L, Wu J, Song S, et al. Plasma exosome-derived sentrin SUMO-specific protease 1: a prognostic biomarker in patients with osteosarcoma. Front Oncol, 2021, 11: 625109.
14.	Han Z, Yi J, Yang Y, et al. SERS and MALDI-TOF MS based plasma exosome profiling for rapid detection of osteosarcoma. Analyst, 2021, 146(21): 6496-6505.
15.	王倩荣, 刘文超, 张红梅. 骨肉瘤血清外泌体整合素β4 水平检测及其与临床病理特征和肺转移的相关性. 现代肿瘤医学, 2022, 30(1): 112-116.
16.	Wu C, Li Z, Feng G, et al. Tumor suppressing role of serum-derived exosomal microRNA-15a in osteosarcoma cells through the GATA binding protein 2/murine double minute 2 axis and the p53 signaling pathway. Bioengineered, 2021, 12(1): 8378-8395.
17.	Han Z, Peng C, Yi J, et al. Matrix-assisted laser desorption ionization mass spectrometry profiling of plasma exosomes evaluates osteosarcoma metastasis. iScience, 2021, 24(8): 102906.
18.	Wang J, Zhang H, Sun X, et al. Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients. J Nanobiotechnology, 2020, 18(1): 151.
19.	Li M, Li S, Du C, et al. Exosomes from different cells: characteristics, modifications, and therapeutic applications. Eur J Med Chem, 2020, 207: 112784.
20.	Lin L, Wang H, Guo W, et al. Osteosarcoma-derived exosomal miR-501-3p promotes osteoclastogenesis and aggravates bone loss. Cell Signal, 2021, 82: 109935.
21.	Li Y, Lin S, Xie X, et al. 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.
22.	Zhang L, Xue L, Wu Y, et al. Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma. Bioengineered, 2021, 12(2): 9520-9530.
23.	Han F, Pu P, Wang C, et al. Osteosarcoma cell-derived exosomal miR-1307 promotes tumorgenesis via targeting AGAP1. Biomed Res Int, 2021, 2021: 7358153.
24.	Zhang Y, Liu Z, Yang X, et al. H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts. Theranostics, 2021, 11(3): 1473-1492.
25.	Cheng Z, Wang L, Wu C, et al. Tumor-derived exosomes induced M2 macrophage polarization and promoted the metastasis of osteosarcoma cells through Tim-3. Arch Med Res, 2021, 52(2): 200-210.
26.	Raimondi L, De Luca A, Gallo A, et al. Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs. Carcinogenesis, 2020, 41(5): 666-677.
27.	Wolf-Dennen K, Gordon N, Kleinerman ES. Exosomal communication by metastatic osteosarcoma cells modulates alveolar macrophages to an M2 tumor-promoting phenotype and inhibits tumoricidal functions. Oncoimmunology, 2020, 9(1): 1747677.
28.	Logozzi M, Mizzoni D, Angelini DF, et al. Microenvironmental pH and exosome levels interplay in human cancer cell lines of different histotypes. Cancers (Basel), 2018, 10(10): 370.
29.	Troyer RM, Ruby CE, Goodall CP, et al. Exosomes from osteosarcoma and normal osteoblast differ in proteomic cargo and immunomodulatory effects on T cells. Exp Cell Res, 2017, 358(2): 369-376.
30.	Gong L, Bao Q, Hu C, et al. Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1. Biochem Biophys Res Commun, 2018, 500(2): 170-176.
31.	Zhou J, Xu L, Yang P, et al. The exosomal transfer of human bone marrow mesenchymal stem cell-derived miR-1913 inhibits osteosarcoma progression by targeting NRSN2. Am J Transl Res, 2021, 13(9): 10178-10192.
32.	Zhang H, Wang J, Ren T, et al. Bone marrow mesenchymal stem cell-derived exosomal miR-206 inhibits osteosarcoma progression by targeting TRA2B. Cancer Lett, 2020, 490: 54-65.
33.	Ge X, Liu W, Zhao W, et al. Exosomal transfer of LCP1 promotes osteosarcoma cell tumorigenesis and metastasis by activating the JAK2/STAT3 signaling pathway. Mol Ther Nucleic Acids, 2020, 21: 900-915.
34.	Qin F, Tang H, Zhang Y, et al. Bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-208a promotes osteosarcoma cell proliferation, migration, and invasion. J Cell Physiol, 2020, 235(5): 4734-4745.
35.	Wang Y, Chu Y, Li K, et al. Exosomes Secreted by adipose-derived mesenchymal stem cells foster metastasis and osteosarcoma proliferation by increasing COLGALT2 expression. Front Cell Dev Biol, 2020, 8: 353.
36.	Huang Y, Liu W, He B, et al. Exosomes derived from bone marrow mesenchymal stem cells promote osteosarcoma development by activating oncogenic autophagy. J Bone Oncol, 2020, 21: 100280.
37.	Zhao W, Qin P, Zhang D, et al. Long non-coding RNA PVT1 encapsulated in bone marrow mesenchymal stem cell-derived exosomes promotes osteosarcoma growth and metastasis by stabilizing ERG and sponging miR-183-5p. Aging (Albany NY), 2019, 11(21): 9581-9596.
38.	Du M, Gu J, Liu C, et al. Genome-wide CRISPR screen identified Rad18 as a determinant of doxorubicin sensitivity in osteosarcoma. J Exp Clin Cancer Res, 2022, 41(1): 154.
39.	Huang X, Wu W, Jing D, et al. Engineered exosome as targeted lncRNA MEG3 delivery vehicles for osteosarcoma therapy. J Control Release, 2022, 343: 107-117.
40.	Wei H, Chen J, Wang S, et al. A nanodrug consisting of doxorubicin and exosome derived from mesenchymal stem cells for osteosarcoma treatment in vitro. Int J Nanomedicine, 2019, 14: 8603-8610.
41.	Wei H, Chen F, Chen J, et al. Mesenchymal stem cell derived exosomes as nanodrug carrier of doxorubicin for targeted osteosarcoma therapy via SDF1-CXCR4 axis. Int J Nanomedicine, 2022, 17: 3483-3495.

1. Gurunathan S, Kang MH, Kim JH. A comprehensive review on factors influences biogenesis, functions, therapeutic and clinical implications of exosomes. Int J Nanomedicine, 2021, 16: 1281-1312.
2. Gill J, Gorlick R. Advancing therapy for osteosarcoma. Nat Rev Clin Oncol, 2021, 18(10): 609-624.
3. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478): eaau6977.
4. Li C, Teixeira AF, Zhu HJ, et al. Cancer associated-fibroblast-derived exosomes in cancer progression. Mol Cancer, 2021, 20(1): 154.
5. Murillo OD, Thistlethwaite W, Rozowsky J, et al. exRNA atlas analysis reveals distinct extracellular RNA cargo types and their carriers present across human biofluids. Cell, 2019, 177(2): 463-477.e15.
6. Tang XH, Guo T, Gao XY, et al. Exosome-derived noncoding RNAs in gastric cancer: functions and clinical applications. Mol Cancer, 2021, 20(1): 99.
7. Yang J, Hu Y, Wang L, et al. Human umbilical vein endothelial cells derived-exosomes promote osteosarcoma cell stemness by activating notch signaling pathway. Bioengineered, 2021, 12(2): 11007-11017.
8. Kersten K, Hu KH, Combes AJ, et al. Spatiotemporal co-dependency between macrophages and exhausted CD8⁺ T cells in cancer. Cancer Cell, 2022, 40(6): 624-638.e9.
9. Zhang H, Yu Y, Wang J, et al. Macrophages-derived exosomal lncRNA LIFR-AS1 promotes osteosarcoma cell progression via miR-29a/NFIA axis. Cancer Cell Int, 2021, 21(1): 192.
10. Cersosimo F, Lonardi S, Bernardini G, et al. Tumor-associated macrophages in osteosarcoma: from mechanisms to therapy. Int J Mol Sci, 2020, 21(15): 5207.
11. Liu W, Long Q, Zhang W, et al. miRNA-221-3p derived from M2-polarized tumor-associated macrophage exosomes aggravates the growth and metastasis of osteosarcoma through SOCS3/JAK2/STAT3 axis. Aging (Albany NY), 2021, 13(15): 19760-19775.
12. Ye Z, Zheng Z, Peng L. MicroRNA profiling of serum exosomes in patients with osteosarcoma by high-throughput sequencing. J Investig Med, 2020, 68(4): 893-901.
13. Wang L, Wu J, Song S, et al. Plasma exosome-derived sentrin SUMO-specific protease 1: a prognostic biomarker in patients with osteosarcoma. Front Oncol, 2021, 11: 625109.
14. Han Z, Yi J, Yang Y, et al. SERS and MALDI-TOF MS based plasma exosome profiling for rapid detection of osteosarcoma. Analyst, 2021, 146(21): 6496-6505.
15. 王倩荣, 刘文超, 张红梅. 骨肉瘤血清外泌体整合素β4 水平检测及其与临床病理特征和肺转移的相关性. 现代肿瘤医学, 2022, 30(1): 112-116.
16. Wu C, Li Z, Feng G, et al. Tumor suppressing role of serum-derived exosomal microRNA-15a in osteosarcoma cells through the GATA binding protein 2/murine double minute 2 axis and the p53 signaling pathway. Bioengineered, 2021, 12(1): 8378-8395.
17. Han Z, Peng C, Yi J, et al. Matrix-assisted laser desorption ionization mass spectrometry profiling of plasma exosomes evaluates osteosarcoma metastasis. iScience, 2021, 24(8): 102906.
18. Wang J, Zhang H, Sun X, et al. Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients. J Nanobiotechnology, 2020, 18(1): 151.
19. Li M, Li S, Du C, et al. Exosomes from different cells: characteristics, modifications, and therapeutic applications. Eur J Med Chem, 2020, 207: 112784.
20. Lin L, Wang H, Guo W, et al. Osteosarcoma-derived exosomal miR-501-3p promotes osteoclastogenesis and aggravates bone loss. Cell Signal, 2021, 82: 109935.
21. Li Y, Lin S, Xie X, et al. 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.
22. Zhang L, Xue L, Wu Y, et al. Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma. Bioengineered, 2021, 12(2): 9520-9530.
23. Han F, Pu P, Wang C, et al. Osteosarcoma cell-derived exosomal miR-1307 promotes tumorgenesis via targeting AGAP1. Biomed Res Int, 2021, 2021: 7358153.
24. Zhang Y, Liu Z, Yang X, et al. H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts. Theranostics, 2021, 11(3): 1473-1492.
25. Cheng Z, Wang L, Wu C, et al. Tumor-derived exosomes induced M2 macrophage polarization and promoted the metastasis of osteosarcoma cells through Tim-3. Arch Med Res, 2021, 52(2): 200-210.
26. Raimondi L, De Luca A, Gallo A, et al. Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs. Carcinogenesis, 2020, 41(5): 666-677.
27. Wolf-Dennen K, Gordon N, Kleinerman ES. Exosomal communication by metastatic osteosarcoma cells modulates alveolar macrophages to an M2 tumor-promoting phenotype and inhibits tumoricidal functions. Oncoimmunology, 2020, 9(1): 1747677.
28. Logozzi M, Mizzoni D, Angelini DF, et al. Microenvironmental pH and exosome levels interplay in human cancer cell lines of different histotypes. Cancers (Basel), 2018, 10(10): 370.
29. Troyer RM, Ruby CE, Goodall CP, et al. Exosomes from osteosarcoma and normal osteoblast differ in proteomic cargo and immunomodulatory effects on T cells. Exp Cell Res, 2017, 358(2): 369-376.
30. Gong L, Bao Q, Hu C, et al. Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1. Biochem Biophys Res Commun, 2018, 500(2): 170-176.
31. Zhou J, Xu L, Yang P, et al. The exosomal transfer of human bone marrow mesenchymal stem cell-derived miR-1913 inhibits osteosarcoma progression by targeting NRSN2. Am J Transl Res, 2021, 13(9): 10178-10192.
32. Zhang H, Wang J, Ren T, et al. Bone marrow mesenchymal stem cell-derived exosomal miR-206 inhibits osteosarcoma progression by targeting TRA2B. Cancer Lett, 2020, 490: 54-65.
33. Ge X, Liu W, Zhao W, et al. Exosomal transfer of LCP1 promotes osteosarcoma cell tumorigenesis and metastasis by activating the JAK2/STAT3 signaling pathway. Mol Ther Nucleic Acids, 2020, 21: 900-915.
34. Qin F, Tang H, Zhang Y, et al. Bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-208a promotes osteosarcoma cell proliferation, migration, and invasion. J Cell Physiol, 2020, 235(5): 4734-4745.
35. Wang Y, Chu Y, Li K, et al. Exosomes Secreted by adipose-derived mesenchymal stem cells foster metastasis and osteosarcoma proliferation by increasing COLGALT2 expression. Front Cell Dev Biol, 2020, 8: 353.
36. Huang Y, Liu W, He B, et al. Exosomes derived from bone marrow mesenchymal stem cells promote osteosarcoma development by activating oncogenic autophagy. J Bone Oncol, 2020, 21: 100280.
37. Zhao W, Qin P, Zhang D, et al. Long non-coding RNA PVT1 encapsulated in bone marrow mesenchymal stem cell-derived exosomes promotes osteosarcoma growth and metastasis by stabilizing ERG and sponging miR-183-5p. Aging (Albany NY), 2019, 11(21): 9581-9596.
38. Du M, Gu J, Liu C, et al. Genome-wide CRISPR screen identified Rad18 as a determinant of doxorubicin sensitivity in osteosarcoma. J Exp Clin Cancer Res, 2022, 41(1): 154.
39. Huang X, Wu W, Jing D, et al. Engineered exosome as targeted lncRNA MEG3 delivery vehicles for osteosarcoma therapy. J Control Release, 2022, 343: 107-117.
40. Wei H, Chen J, Wang S, et al. A nanodrug consisting of doxorubicin and exosome derived from mesenchymal stem cells for osteosarcoma treatment in vitro. Int J Nanomedicine, 2019, 14: 8603-8610.
41. Wei H, Chen F, Chen J, et al. Mesenchymal stem cell derived exosomes as nanodrug carrier of doxorubicin for targeted osteosarcoma therapy via SDF1-CXCR4 axis. Int J Nanomedicine, 2022, 17: 3483-3495.

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