Exploring the Role of Osteosarcoma-Derived Extracellular Vesicles in Pre-Metastatic Niche Formation and Metastasis in the 143-B Xenograft Mouse Osteosarcoma Model
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The pre-metastatic niche (PMN) is a tumor-driven microenvironment in distant organs that can foster and support the survival and growth of disseminated tumor cells. This facilitates the establishment of secondary lesions that eventually form overt metastasis, the main cause of cancer-related death. In recent years, tumor-derived extracellular-vesicles (EVs) have emerged as potentially key drivers of the PMN. The role of the PMN in osteosarcoma metastasis is poorly understood and the potential contribution of osteosarcoma cell-derived EVs to PMN formation has not been investigated so far. Here, we characterize pulmonary PMN development using the spontaneously metastasizing 143-B xenograft osteosarcoma mouse model. We demonstrate the accumulation of CD11b+ myeloid cells in the pre-metastatic lungs of tumor-bearing mice. We also establish that highly metastatic 143-B and poorly metastatic SAOS-2 osteosarcoma cell-derived EV education in naïve mice can recapitulate the recruitment of myeloid cells to the lungs. Surprisingly, despite EV-induced myeloid cell infiltration in the pre-metastatic lungs, 143-B and SAOS-2 EVs do not contribute towards the 143-B metastatic burden in the context of both spontaneous as well as experimental metastasis in severe-combined immunodeficient (SCID) mice. Taken together, OS-derived EVs alone may not be able to form a functional PMN, and may perhaps require a combination of tumor-secreted factors along with EVs to do so. Additionally, our study gives a valuable insight into the PMN complexity by providing the transcriptomic signature of the premetastatic lungs in an osteosarcoma xenograft model for the first time. In conclusion, identification of regulators of cellular and molecular changes in the pre-metastatic lungs might lead to the development of a combination therapies in the future that interrupt PMN formation and combat osteosarcoma metastasis.
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Extracellular vesicles released from osteosarcoma cells manipulate the lung environment at a distance and prepare the pre-metastatic niche to host migrating tumour cells.
“Extracellular vesicles released from osteosarcoma cells manipulate the lung environment at a distance and prepare the pre-metastatic niche to host migrating tumour cells 56 .”
From Osteosarcoma (2022) · cites this paper as [56]
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- Authors
- Mazumdar, A., Urdinez, J., Boro, A., Arlt, M. J. E., Egli, F. E., Niederöst, B., Jaeger, P. K., Moschini, G., 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)
- Corresponding author
- Gvozdenovic, Ana
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2020-11-20
- Volume
- 12
- Issue
- 11
- Pages
- 3457
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC7699714
- OpenAlex
- W3101287026
- Cited by
- 40
- References
- 66
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 10 · 2022: 7 · 2021: 6
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- 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
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Keywords
- osteosarcoma, extracellular vesicles, pre-metastatic niche, metastasis, lung metastasis, myeloid cell recruitment, CD11b+ myeloid cells, Saos-2 cells, tumor microenvironment, gene expression signatures, xenograft mouse model, SCID mice
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