CoChat
Sign Up
Cited by 55Extracellular vesicles in diseaseMesenchymal stem cell researchSarcoma Diagnosis and Treatment

Exosomes derived from bone marrow mesenchymal stem cells promote osteosarcoma development by activating oncogenic autophagy

Open access
Huang, Yao, Liu, Wei, He, Bing, Wang, Lei, Zhang, Fucheng, Shu, Hao, Sun, Luning·2020·Journal of Bone Oncology
DOI 10.1016/j.jbo.2020.100280PMC PMC7019122
Open this paper in CoChat — free accountOpen PDF

Abstract

Osteosarcoma (OS) is a malignant bone tumor that frequently occurs in adolescents. It has a high rate of pulmonary metastasis and mortality. Previous studies have demonstrated that human bone marrow mesenchymal stem cells (hBMSCs) can promote the malignant progression in various tumors, including OS. Also, it is recognized that exosomes derived from hBMSCs (hBMSC-Exos) mediate cell-to-cell communication and exhibit similar effects on the development of various tumors. However, the role of hBMSC-Exos in the development of OS is still unclear and the underlying mechanism needs to be elucidated. Our results show that hBMSC-derived exosomes promote OS cell proliferation, migration, and invasion. Meanwhile, silencing autophagy-related gene 5 (ATG5) in OS cells abolishes the pro-tumor effects of hBMSC-Exos in vitro and in vivo. Our present study demonstrates that hBMSC-Exos promotes tumorigenesis and metastasis by promoting oncogenic autophagy in OS.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.jbo.2020.100280

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Silencing autophagy-related gene 5 in OS cells eliminates the pro-tumor influence of BM-MSC exosomes both in vivo and in vitro.

    “However, if the autophagy-related gene 5 is silenced in OS cells, it eliminates the pro-tumor influence of BM-MSC exosomes both in vivo and in vitro [122].”

    From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [122]

    The Results report that ATG5 silencing abolished the exosome-induced effects on OS-cell proliferation, migration, and invasion in vitro, and reduced tumor growth and lung metastasis in vivo. But the Discussion explicitly says siATG5 did not totally abolish exosome-mediated tumorigenesis. Thus, “eliminates” overstates the in vivo finding and the paper’s overall conclusion. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • BM-MSC-derived exosomes may boost osteosarcoma development by promoting oncogenic autophagy in nude mice.

    “Also, BM-MSC-derived exosomes may boost osteosarcoma development by promoting oncogenic autophagy in nude mice [122].”

    From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [122]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 29

  1. [1]Berner K. Johannesen T.B. Berner A. Haugland H.K. Bjerkehagen B. Bohler P.J. Bruland O.S. Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma Acta Oncol. 54 2015 25 33 24957555 PMC4364276
  2. [2]Aljubran A.H. Griffin A. Pintilie M. Blackstein M. Osteosarcoma in adolescents and adults: survival analysis with and without lung metastases Ann. Oncol. 20 2009 1136 1141 19153114
  3. [3]Gill J. Ahluwalia M.K. Geller D. Gorlick R. New targets and approaches in osteosarcoma Pharmacol. Ther. 137 2013 89 99 22983152
  4. [4]Kucerova L. Altanerova V. Matuskova M. Tyciakova S. Altaner C. Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy Cancer Res. 67 2007 6304 6313 17616689
  5. [5]Yu J.M. Jun E.S. Bae Y.C. Jung J.S. Mesenchymal stem cells derived from human adipose tissues favor tumor cell growth in vivo Stem Cells Dev. 17 2008 463 473 18522494
  6. [6]Yu F.X. Hu W.J. He B. Zheng Y.H. Zhang Q.Y. Chen L. Bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion World J. Surg. Oncol. 13 2015 52 25890096 PMC4334855
  7. [7]Xiao W. Mohseny A.B. Hogendoorn P.C. Cleton-Jansen A.M. Mesenchymal stem cell transformation and sarcoma genesis Clin. Sarcoma Res. 3 2013 10 23880362 PMC3724575
  8. [8]Tirode F. Laud-Duval K. Prieur A. Delorme B. Charbord P. Delattre O. Mesenchymal stem cell features of Ewing tumors Cancer Cell 11 2007 421 429 17482132
  9. [9]Raposo G. Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends J. Cell Biol. 200 2013 373 383 23420871 PMC3575529
  10. [10]Mathieu M. Martin-Jaular L. Lavieu G. Thery C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication Nat. Cell Biol. 21 2019 9 17 30602770
  11. [11]Nawaz M. Fatima F. Vallabhaneni K.C. Penfornis P. Valadi H. Ekstrom K. Kholia S. Whitt J.D. Fernandes J.D. Pochampally R. Squire J.A. Camussi G. Extracellular vesicles: evolving factors in stem cell biology Stem Cells Int. 2016 1073140 2016 PMC4663346 26649044
  12. [12]Tan X. Gong Y.Z. Wu P. Liao D.F. Zheng X.L. Mesenchymal stem cell-derived microparticles: a promising therapeutic strategy Int. J. Mol. Sci. 15 2014 14348 14363 25196436 PMC4159854
  13. [13]Kidd S. Spaeth E. Dembinski J.L. Dietrich M. Watson K. Klopp A. Battula V.L. Weil M. Andreeff M. Marini F.C. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging Stem Cells 27 2009 2614 2623 19650040 PMC4160730
  14. [14]Zhu W. Xu W. Jiang R. Qian H. Chen M. Hu J. Cao W. Han C. Chen Y. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo Exp. Mol. Pathol. 80 2006 267 274 16214129
  15. [16]Liu W. Wang Y. Gong F. Rong Y. Luo Y. Tang P. Zhou Z. Zhou Z. Xu T. Jiang T. Yang S. Yin G. Chen J. Fan J. Cai W. Exosomes derived from bone mesenchymal stem cells repair traumatic spinal cord injury by suppressing the activation of A1 neurotoxic reactive astrocytes J. Neurotrauma 36 2019 469 484 29848167
  16. [17]Luetke A. Meyers P.A. Lewis I. Juergens H. Osteosarcoma treatment – where do we stand? A state of the art review Cancer Treat. Rev. 40 2014 523 532 24345772
  17. [18]Liu W. Zhou Z. Zhang Q. Rong Y. Li L. Luo Y. Wang J. Yin G. Lv C. Cai W. Overexpression of miR-1258 inhibits cell proliferation by targeting AKT3 in osteosarcoma Biochem. Biophys. Res. Commun. 510 2019 479 486 30737029
  18. [19]Luo Y. Liu W. Tang P. Jiang D. Gu C. Huang Y. Gong F. Rong Y. Qian D. Chen J. Zhou Z. Zhao S. Wang J. Xu T. Wei Y. Yin G. Fan J. Cai W. miR-624-5p promoted tumorigenesis and metastasis by suppressing hippo signaling through targeting PTPRB in osteosarcoma cells J. Exp. Clin. Cancer Res. 38 2019 488 31829261 PMC6907337
  19. [20]Zhu W. Huang L. Li Y. Zhang X. Gu J. Yan Y. Xu X. Wang M. Qian H. Xu W. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo Cancer Lett. 315 2012 28 37 22055459
  20. [21]Ono M. Kosaka N. Tominaga N. Yoshioka Y. Takeshita F. Takahashi R.U. Yoshida M. Tsuda H. Tamura K. Ochiya T. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells Sci. Signal. 7 2014 ra63 24985346
  21. [22]Gu H. Ji R. Zhang X. Wang M. Zhu W. Qian H. Chen Y. Jiang P. Xu W. Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway Mol. Med. Rep. 14 2016 3452 3458 27513187
  22. [23]Shi S. Zhang Q. Xia Y. You B. Shan Y. Bao L. Li L. You Y. Gu Z. Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression Am. J. Cancer Res. 6 2016 459 472 27186416 PMC4859673
  23. [24]Singh S.S. Vats S. Chia A.Y. Tan T.Z. Deng S. Ong M.S. Arfuso F. Yap C.T. Goh B.C. Sethi G. Huang R.Y. Shen H.M. Manjithaya R. Kumar A.P. Dual role of autophagy in hallmarks of cancer Oncogene 37 2018 1142 1158 29255248
  24. [26]Codogno P. Meijer A.J. Atg5: more than an autophagy factor Nat. Cell Biol. 8 2006 1045 1047 17013414
  25. [27]Zhao Z.J. Fux B. Goodwin M. Dunay I.R. Strong D. Miller B.C. Cadwell K. Delgado M.A. Ponpuak M. Green K.G. Schmidt R.E. Mizushima N. Deretic V. Sibley L.D. Virgin H.W. Autophagosome-independent Essential Function for the Autophagy Protein Atg5 in Cellular Immunity to Intracellular Pathogens Cell Host Microbe 4 2008 458 469 18996346 PMC2682425
  26. [29]Liu W. Li L. Rong Y. Qian D. Chen J. Zhou Z. Luo Y. Jiang D. Cheng L. Zhao S. Kong F. Wang J. Zhou Z. Xu T. Gong F. Huang Y. Gu C. Zhao X. Bai J. Wang F. Zhao W. Zhang L. Li X. Yin G. Fan J. Cai W. Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126 Acta Biomater. 2019 31857259
  27. [30]Che Y. Shi X. Shi Y. Jiang X. Ai Q. Shi Y. Gong F. Jiang W. Exosomes derived from miR-143-overexpressing MSCs inhibit cell migration and invasion in human prostate cancer by downregulating TFF3 Mol. Ther. Nucl. Acids 18 2019 232 244 PMC6796755 31563120
  28. [31]Gong L. Bao Q. Hu C. Wang J. Zhou Q. Wei L. Tong L. Zhang W. Shen Y. Exosomal miR-675 from metastatic osteosarcoma promotes cell migration and invasion by targeting CALN1 Biochem. Biophys. Res. Commun. 500 2018 170 176 29626470
  29. [32]Mao Y. Wang Y. Dong L. Zhang Y. Zhang Y. Wang C. Zhang Q. Yang S. Cao L. Zhang X. Li X. Fu Z. Hypoxic exosomes facilitate angiogenesis and metastasis in esophageal squamous cell carcinoma through altering the phenotype and transcriptome of endothelial cells J. Exp. Clin. Cancer Res. 38 2019 389 31488217 PMC6727585

Cited by

Sorted by citations

Authors
Huang, Y., Liu, W., He, B., Wang, L., Zhang, F., Shu, H., & Sun, L.
Affiliations
  • Nanjing University of Chinese Medicine (CN)
  • Jiangsu Province Hospital (CN)
Corresponding author
Sun, Luning
ORCID
Venue
Journal of Bone Oncology
Publisher
Elsevier BV
Published
2020-04
Volume
21
Pages
100280
ISSN
  • 2212-1366 (ISSN-L)
  • 2212-1374
DOI
10.1016/j.jbo.2020.100280
PMC
PMC7019122
OpenAlex
W3005213790
Cited by
55
References
4
Citations by year
2026: 4 · 2025: 3 · 2024: 4 · 2023: 11 · 2022: 14 · 2021: 16 · 2020: 3
FWCI
3.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of bone oncology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Natural Science Foundation of Jiangsu Province
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
Keywords
osteosarcoma, exosomes, bone marrow mesenchymal stem cells, ATG5, tumor cell proliferation, cell migration and invasion, metastasis, tumor microenvironment, cell-to-cell communication

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review