Targeting Oncofoetal Chondroitin Sulphate Allows Identification of Tumour‐Derived Extracellular Vesicles

PMCID: PMC12173530

PMID: 40527727

DOI: 10.1002/jev2.70106

Journal: Journal of extracellular vesicles

Publication Date: 2025-6-17

Authors: Enciso‐Martinez A, Løppke C, Koene JJ, Ebbelaar J, van der Geest M, et al.

Key Points

• First comprehensive method for specifically identifying tumor-derived extracellular vesicles using oncofoetal chondroitin sulphate
• Demonstrated ofCS detection across 6 different cancer cell lines with varying intensity levels
• Provides a promising new approach for potential cancer biomarker detection and characterization

Summary

This groundbreaking study introduces a novel method for identifying tumor-derived extracellular vesicles (tdEVs) using oncofoetal chondroitin sulphate (ofCS), a malignancy-associated glycosaminoglycan modification. By leveraging the malaria VAR2CSA protein (rVAR2), researchers developed a highly specific fluorescent labeling technique that can detect cancer-associated extracellular vesicles across multiple cancer types, including lung, pancreatic, colorectal, ovarian, glioblastoma, and melanoma.

The researchers demonstrated remarkable precision in tdEV identification through multiple advanced imaging techniques, including super-resolution fluorescence microscopy, flow cytometry, and cryo-electron microscopy. Critically, the method showed consistent results across different experimental conditions, with rVAR2 specifically binding to ofCS and maintaining detection capabilities even after epithelial-to-mesenchymal transition. In a preliminary proof-of-concept study with pancreatic adenocarcinoma patients, four out of five patients exhibited higher rVAR2 staining compared to healthy controls, suggesting significant potential for future diagnostic applications.