Extracellular vesicle heterogeneity through the lens of multiomics
Extracellular vesicles (EVs) are heterogeneous in size, biogenesis, content, and function. Aggressive cancer cells release a distinct, poorly characterized, and particularly large EV subtype, namely large oncosomes (LOs). This study employs an optimized method to improve LO yields and integrates mass spectrometry and RNA sequencing (RNA-seq) to profile their molecular cargo. A consistent set of proteins enriched in LOs is identified across glioma, prostate, and breast cancer cell lines. These proteins are also present as mRNA in LOs from the prostate cancer model and are abundant in plasma LOs from 20 patients with metastasis. Single-LO RNA-seq confirms bulk LO cargo, demonstrating the utility of single-cell technologies for large vesicle analysis. Our patient study provides proof-of-principle evidence that we can use multiomics to delve into EV heterogeneity, biogenesis, and composition. It also suggests that plasma LOs help stratify patients, supporting their potential prognostic value for developing a multi-analyte approach for liquid biopsy.
Authors
- Yari Ciani (ORCID: https://orcid.org/0000-0002-9635-2830)
- Jennifer E. Van Eyk (ORCID: https://orcid.org/0000-0001-9050-148X)
- Paul C. Boutros (ORCID: https://orcid.org/0000-0003-0553-7520)
- Sarah J. Parker (ORCID: https://orcid.org/0000-0001-8911-3615)
- John P. Nolan (ORCID: https://orcid.org/0000-0002-9669-382X)
- Jlenia Guarnerio (ORCID: https://orcid.org/0000-0001-7576-7095)
- Andries Zijlstra (ORCID: https://orcid.org/0000-0001-8460-8803)
- Megan Hall (ORCID: https://orcid.org/0000-0002-2289-0732)
- Elizabeth Hutchins (ORCID: https://orcid.org/0000-0003-2543-0798)
- Clotilde Théry (ORCID: https://orcid.org/0000-0001-8294-6884)
- Wei Yang (ORCID: https://orcid.org/0000-0003-2575-3570)
- Kendall R. Van Keuren‐Jensen (ORCID: https://orcid.org/0000-0001-8833-6323)
- Edwin M. Posadas (ORCID: https://orcid.org/0000-0001-8649-1346)
- Rebecca Reiman
- Wenyan Zhao (ORCID: https://orcid.org/0000-0003-4588-2724)
- Sungyong You (ORCID: https://orcid.org/0000-0003-3513-1783)
- Dolores Di Vizio (ORCID: https://orcid.org/0000-0002-9787-6556)
- Javier Mariscal (ORCID: https://orcid.org/0000-0002-8741-4956)
- Zhuyu Qiu (ORCID: https://orcid.org/0000-0003-2510-7069)
- Bo Zhou (ORCID: https://orcid.org/0000-0002-7816-7017)
- Ágnes Kittel (ORCID: https://orcid.org/0000-0002-6888-7731)
- Michael R. Freeman (ORCID: https://orcid.org/0000-0001-8142-3432)
- Francesca Demichelis (ORCID: https://orcid.org/0000-0002-8266-8631)
- Taylon Felipe Silva (ORCID: https://orcid.org/0000-0003-3491-2828)
- Shannon L. Stott (ORCID: https://orcid.org/0000-0002-0349-0522)
- Francesca Galasso (ORCID: https://orcid.org/0009-0003-8404-8908)
- Minhyung Kim (ORCID: https://orcid.org/0000-0002-5628-1062)
- Emily Ko (ORCID: https://orcid.org/0000-0002-4893-3227)
- Yang Wang (ORCID: https://orcid.org/0000-0002-6649-5291)
- Fatima Bedier
Institutions
- Cedars-Sinai Medical Center (US)
- Translational Genomics Research Institute (US)
- Inserm (FR)
- University of California, Los Angeles (US)
- University of Trento (IT)
- Université Paris Sciences et Lettres (FR)
- Massachusetts General Hospital (US)
- HUN-REN Institute of Experimental Medicine (HU)
- USC Norris Comprehensive Cancer Center (US)
- Cedars-Sinai Smidt Heart Institute (US)
- Center for Systems Biology (US)
- Scintillon Institute (US)
- Institut Curie (FR)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-06-06
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102161
- Citations
- 21
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 16.93
Funders
- Cedars-Sinai Medical Center
- Cancer Research UK
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health