Faculty, Staff and Student Publications
Publication Date
3-1-2025
Journal
Journal of Extracellular Biology
Abstract
Several reports have demonstrated that CD147, an N-glycosylated protein that is exchanged by cells in soluble form or through small extracellular vesicles (sEVs), can promote cancer progression. However, its activity related to EVs in colorectal cancer (CRC) is still not fully understood. Previously, we showed that sEV secretion during CRC stem cell (CR-CSCs) differentiation is partially controlled by CD147, and that CD147-expressing sEVs (sEVs-CD147) activate a signalling cascade in recipient cells, inducing molecular invasive features in CR-CSCs. In the present study, we demonstrated that sEVs-CD147 increase the expression of myofibroblast and activation markers in cancer-associated fibroblasts (CAF). In sEVs-CD147-activated CAF, aerobic glycolysis was also triggered by the β-catenin signalling pathway and induced lactate release. These effects were associated with NFKβ upregulation and NO secretion that caused increased cytokines production and VEGF release, respectively. Furthermore, co-culture with CAF promoted CR-CSC invasivity in vitro and tumour growth in vivo. Spatial proteomics analysis confirmed in vivo the activation of fibroblasts and the modulation of their metabolic features, within their biological context, after their conditioning with CD147-expressing sEVs. Our findings indicate that sEV-packaged CD147 is involved in CAF activation, thus promoting tumour progression via stroma metabolism modification.
Keywords
cancer‐associated fibroblasts, CD147, extracellular vesicles, tumour microenvironment
DOI
10.1002/jex2.70039
PMID
40104175
PMCID
PMC11913892
PubMedCentral® Posted Date
3-17-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons