Sarcoma-Derived Extracellular Vesicles: From Biology to Clinical Translation
5 affiliations
- 1Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, 460 W 10th Ave, Columbus, OH 43210, USA
- 2Department of Retroperitoneal and Soft Tissue Surgical Oncology, Fudan University Zhongshan Hospital, No. 180 Fenglin Rd, Shanghai 200032, China
- 3College of Arts and Sciences, The Ohio State University, 100 Denney Hall, 164 Annie and John Glenn Avenue, Columbus, OH 43210, USA
- 4Department of Mechanical and Aerospace Engineering, The Ohio State University, 201 W 19th Ave, Columbus, OH 43210, USA
- 5Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, 460 W 12th Ave, Columbus, OH 43210, USA
Abstract
Sarcomas constitute a heterogeneous group of rare mesenchymal malignancies encompassing soft tissue and bone sarcomas, whose histological and molecular diversity poses substantial challenges for early diagnosis, disease surveillance, and clinical management. Extracellular vesicles (EVs) are membrane-bound particles that mediate intercellular communication via delivery of bioactive cargo including proteins, nucleic acids, and lipids, and have emerged as promising analytes for minimally invasive liquid biopsy. While the biological functions and clinical value of EVs have been extensively characterized in common epithelial cancers, investigations focusing on sarcoma-derived EVs remain relatively limited and unevenly distributed across histological subtypes. Emerging evidence suggests that EV cargo can reflect molecular features of different sarcoma subtypes, including gene amplifications, fusion transcripts, miRNAs, lncRNAs, and tumor-associated proteins. This review provides an overview of current advances in sarcoma-derived EV research. We outline the classification of EV subtypes and their molecular cargo characteristics, with emphasis on features particularly relevant to sarcoma biology and biomarker development, as well as the technical principles, advantages, and limitations of EV isolation methodologies. We then focus on the roles of sarcoma-derived EVs in mediating tumor-host crosstalk, including facilitating the establishment of the pre-metastatic niche, promoting immunosuppression and immune evasion, and remodeling the tumor microenvironment. We further summarize emerging translational applications of sarcoma-derived EVs, covering their utility as circulating biomarkers for disease diagnosis, longitudinal monitoring, and treatment response assessment, as well as their potential as therapeutic targets for anti-tumor intervention. Where direct evidence in sarcoma remains limited, we distinguish findings established in sarcoma models from mechanisms extrapolated from other malignancies. Finally, we discuss current challenges to clinical translation, including small patient cohorts, lack of standardized technical protocols, and underrepresentation of rare histological subtypes. We propose that standardized EV isolation and characterization methods, larger collaborative datasets, and integration of multimodal liquid biopsy approaches will be important for advancing the clinical application of sarcoma-derived EVs and improving disease monitoring and patient management.
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BibTeX
@article{zhang2026sarcomaderived,
title = {{Sarcoma-Derived Extracellular Vesicles: From Biology to Clinical Translation}},
author = {Qi Zhang and Priya Dhawale and Patricia Sarchet and Hanxing Tong and Ali F. Usmani and Premanshu K. Singh and Shaurya Prakash and Yong Zhang and Raphael E. Pollock and Federica Calore},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16111567},
url = {https://www.mdpi.com/2218-273X/16/11/1567},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sarcoma-Derived Extracellular Vesicles: From Biology to Clinical Translation
AU - Qi Zhang
AU - Priya Dhawale
AU - Patricia Sarchet
AU - Hanxing Tong
AU - Ali F. Usmani
AU - Premanshu K. Singh
AU - Shaurya Prakash
AU - Yong Zhang
AU - Raphael E. Pollock
AU - Federica Calore
PY - 2026
DA - 2026/10/28
JO - Biomolecules
DO - 10.3390/biom16111567
UR - https://www.mdpi.com/2218-273X/16/11/1567
AB - Sarcomas constitute a heterogeneous group of rare mesenchymal malignancies encompassing soft tissue and bone sarcomas, whose histological and molecular diversity poses substantial challenges for early diagnosis, disease surveillance, and clinical management. Extracellular vesicles (EVs) are membrane-bound particles that mediate intercellular communication via delivery of bioactive cargo including proteins, nucleic acids, and lipids, and have emerged as promising analytes for minimally invasive liquid biopsy. While the biological functions and clinical value of EVs have been extensively characterized in common epithelial cancers, investigations focusing on sarcoma-derived EVs remain relatively limited and unevenly distributed across histological subtypes. Emerging evidence suggests that EV cargo can reflect molecular features of different sarcoma subtypes, including gene amplifications, fusion transcripts, miRNAs, lncRNAs, and tumor-associated proteins. This review provides an overview of current advances in sarcoma-derived EV research. We outline the classification of EV subtypes and their molecular cargo characteristics, with emphasis on features particularly relevant to sarcoma biology and biomarker development, as well as the technical principles, advantages, and limitations of EV isolation methodologies. We then focus on the roles of sarcoma-derived EVs in mediating tumor-host crosstalk, including facilitating the establishment of the pre-metastatic niche, promoting immunosuppression and immune evasion, and remodeling the tumor microenvironment. We further summarize emerging translational applications of sarcoma-derived EVs, covering their utility as circulating biomarkers for disease diagnosis, longitudinal monitoring, and treatment response assessment, as well as their potential as therapeutic targets for anti-tumor intervention. Where direct evidence in sarcoma remains limited, we distinguish findings established in sarcoma models from mechanisms extrapolated from other malignancies. Finally, we discuss current challenges to clinical translation, including small patient cohorts, lack of standardized technical protocols, and underrepresentation of rare histological subtypes. We propose that standardized EV isolation and characterization methods, larger collaborative datasets, and integration of multimodal liquid biopsy approaches will be important for advancing the clinical application of sarcoma-derived EVs and improving disease monitoring and patient management.
SN - 2218-273X
ER -