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Cited by 71Extracellular vesicles in diseaseCancer Cells and MetastasisTGF-β signaling in diseases

Osteosarcoma-Derived Extracellular Vesicles Induce Lung Fibroblast Reprogramming

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Mazumdar, Alekhya, Urdinez, Joaquin, Boro, Aleksandar, Migliavacca, Jessica, Arlt, Matthias J.E., Muff, Roman, Fuchs, Bruno, Snedeker, Jess Gerrit +1 more·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21155451PMC PMC7432951
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Abstract

Tumor-secreted extracellular vesicles (EVs) have been identified as mediators of cancer–host intercellular communication and shown to support pre-metastatic niche formation by modulating stromal cells at future metastatic sites. While osteosarcoma, the most common primary malignant bone tumor in children and adolescents, has a high propensity for pulmonary metastases, the interaction of osteosarcoma cells with resident lung cells remains poorly understood. Here, we deliver foundational in vitro evidence that osteosarcoma cell-derived EVs drive myofibroblast/cancer-associated fibroblast differentiation. Human lung fibroblasts displayed increased invasive competence, in addition to increased α-smooth muscle actin expression and fibronectin production upon EV treatment. Furthermore, we demonstrate, through the use of transforming growth factor beta receptor 1 (TGFBR1) inhibitors and CRISPR-Cas9-mediated knockouts, that TGFβ1 present in osteosarcoma cell-derived EVs is responsible for lung fibroblast differentiation. Overall, our study highlights osteosarcoma-derived EVs as novel regulators of lung fibroblast activation and provides mechanistic insight into how osteosarcoma cells can modulate distant cells to potentially support metastatic progression.

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  • TAFs can be reprogrammed in lung under the influence of TGF-β1 in osteosarcoma-derived EVs, which promotes metastatic progression of osteosarcoma.

    “TAFs can be reprogrammed in lung under the influence of TGF-β1 in osteosarcoma-derived EVs, which promotes metastatic progression of osteosarcoma [51].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [51]

    The Discussion reports that osteosarcoma EV-associated TGFβ1 drives lung fibroblast activation and differentiation toward a myofibroblast/CAF phenotype in vitro. The paper describes support for metastatic progression as potential, not as a demonstrated consequence of that reprogramming in the lung. (LLM, conf=0.87)

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Cited by

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Authors
Mazumdar, A., Urdinez, J., Boro, A., Migliavacca, J., Arlt, M. J. E., Muff, R., Fuchs, B., Snedeker, J. G., & Gvozdenovic, A.
Affiliations
  • ETH Zurich (CH)
  • Department of Orthopedics, Balgrist University Hospital, CH-8008 Zurich, Switzerland
  • Universitätsklinik Balgrist (CH)
  • University Children's Hospital Zurich (CH)
Corresponding author
Gvozdenovic, Ana
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-07-30
Volume
21
Issue
15
Pages
5451
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21155451
PMC
PMC7432951
OpenAlex
W3046141052
Cited by
71
References
1
Citations by year
2026: 10 · 2025: 14 · 2024: 12 · 2023: 14 · 2022: 11 · 2021: 9 · 2020: 1
FWCI
2.84
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection (cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
Universität Zürich
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
osteosarcoma, extracellular vesicles, lung fibroblasts, cancer-associated fibroblasts, myofibroblast differentiation, TGF-β1, TGFBR1, lung metastasis, tumor microenvironment, fibroblast reprogramming, alpha-smooth muscle actin, fibronectin, stromal-epithelial interactions
MeSH terms
Extracellular Vesicles, Receptor, Transforming Growth Factor-beta Type I, Actins, Fibroblasts, Humans, Lung, Neoplasm Invasiveness, Neoplasm Metastasis, Osteosarcoma, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, CRISPR-Cas Systems, Cellular Reprogramming

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