TY - JOUR
T1 - Mesenchymal Colorectal Cancers Secrete Vesicles With Unique Cargo That Can Be Used for Liquid Biopsy Based Diagnostics
AU - Asif, Paris J.
AU - Borghuis, Lauri H.
AU - van Hooff, Sander R.
AU - Grootemaat, Anita E.
AU - van Eijndhoven, Monique A. J.
AU - de Rooij, Johan
AU - Groenewegen, Nils J.
AU - Boza, Jennifer Perez
AU - Kranenburg, Onno
AU - Rinkes, Inne H. M. Borel
AU - Gómez-Martín, Cristina
AU - Pruijt, Hans F. M.
AU - van der Wel, Nicole N.
AU - Torang, Arezo
AU - Buffart, Tineke E.
AU - Pegtel, D. Michiel
AU - Medema, Jan Paul
N1 - Publisher Copyright:
© 2025 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.
PY - 2025/11/1
Y1 - 2025/11/1
N2 - Tumour-derived extracellular vesicles (TEVs) play a crucial role in cancer progression, metastasis and therapy resistance but their distinct profiles across different cancer stages and molecular subtypes remain underexplored. This study initially analysed TEVs from all CMS subtypes in colorectal cancer (CRC) cells and continued focusing on the epithelial (CMS2) and mesenchymal (CMS4) subtypes using six cell lines and clinical samples. Investigation of the cargo of vesicles secreted by the two subtypes revealed significant differences in mRNA, miRNA, and protein profiles between the two subtypes. Notably, CMS2 predominantly secreted smaller, Tetraspanin-8 (TSPAN8) enriched EVs, while CMS4 produced both larger and smaller EVs, enriched in TSPAN4. This underscores the complexity of vesicle heterogeneity between these subtypes. Additionally, we assessed miRNA profiles from plasma-derived bulk TEVs in CRC patients. Our integrative analysis identified a subtype-specific miRNA signature, indicating that TEVs from CMS2 and CMS4 cells can be detected in circulation and may serve as potential diagnostic tool for CRC.
AB - Tumour-derived extracellular vesicles (TEVs) play a crucial role in cancer progression, metastasis and therapy resistance but their distinct profiles across different cancer stages and molecular subtypes remain underexplored. This study initially analysed TEVs from all CMS subtypes in colorectal cancer (CRC) cells and continued focusing on the epithelial (CMS2) and mesenchymal (CMS4) subtypes using six cell lines and clinical samples. Investigation of the cargo of vesicles secreted by the two subtypes revealed significant differences in mRNA, miRNA, and protein profiles between the two subtypes. Notably, CMS2 predominantly secreted smaller, Tetraspanin-8 (TSPAN8) enriched EVs, while CMS4 produced both larger and smaller EVs, enriched in TSPAN4. This underscores the complexity of vesicle heterogeneity between these subtypes. Additionally, we assessed miRNA profiles from plasma-derived bulk TEVs in CRC patients. Our integrative analysis identified a subtype-specific miRNA signature, indicating that TEVs from CMS2 and CMS4 cells can be detected in circulation and may serve as potential diagnostic tool for CRC.
KW - colorectal cancer
KW - consensus molecular subtypes
KW - diagnostic tool
KW - miRNA signature
KW - proteomic analysis
KW - tumour-derived extracellular vesicles
UR - https://www.scopus.com/pages/publications/105020451221
U2 - 10.1002/jev2.70171
DO - 10.1002/jev2.70171
M3 - Article
C2 - 41167980
SN - 2001-3078
VL - 14
JO - Journal of extracellular vesicles
JF - Journal of extracellular vesicles
IS - 11
M1 - e70171
ER -
