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Updated: Nov 14, 2025
In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Extracellular vesicles derived from macrophages display glycyl-tRNA synthetase 1 and exhibit anti-cancer activity
Peter C Goughnour1, Min Chul Park1, Sang Bum Kim1
1Institute for Artificial Intelligence and Biomedical Research Medicinal Bioconvergence Research Center College of Pharmacy & College of Medicine Gangnam Severance Hospital Yonsei University Incheon Korea.
Abstract:
Glycyl-tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20-58 nm (mean diameter: 36.9 nm) and a buoyant density of 1.13-1.17 g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1-containing EVs (GARS1-EVs). Among the identified factors, insulin-like growth factor II receptor, and vimentin also contributed to the anti-cancer activity of GARS1-EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis.
Insights
Macrophages secrete Glycyl-tRNA synthetase 1 (GARS1) via unique extracellular vesicles (EVs). These GARS1-EVs, containing specific proteins, exhibit anti-cancer properties by promoting tumor cell apoptosis.
Area of Science:
- Cell Biology
- Cancer Research
- Immunology
Background:
- Glycyl-tRNA synthetase 1 (GARS1) is a cytosolic enzyme secreted by macrophages.
- GARS1 exhibits pro-apoptotic effects on cancer cells.
- The mechanism of GARS1 secretion remains unclear.
Purpose of the Study:
- To elucidate the mechanism of GARS1 secretion.
- To characterize the extracellular vesicles (EVs) involved in GARS1 secretion.
- To identify other factors within these EVs that contribute to anti-cancer activity.
Main Methods:
- Characterization of extracellular vesicles (EVs) by size and density.
- Analysis of GARS1 anchoring to EVs.
- Proteomic analysis of GARS1-containing EVs (GARS1-EVs).
Main Results:
- GARS1 is secreted via unique EVs (20-58 nm diameter, 1.13-1.17 g/ml density).
- GARS1 is surface-anchored to EVs via palmitoylated C390.
- Proteomic analysis revealed 164 unique proteins in GARS1-EVs, including IGF-II receptor and vimentin, which enhance anti-cancer effects.
Conclusions:
- This study identifies unique secretory vesicles responsible for GARS1 release.
- These GARS1-EVs contain multiple intracellular factors involved in anti-tumor immunity.
- The findings provide insights into a novel mechanism of cancer cell apoptosis induction.
