CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by...

Area of Science:

• Oncology
• Cell Biology
• Cancer Research

Background:

• CD147 protein, found in soluble or extracellular vesicle (EV) forms, is implicated in cancer progression.
• The role of CD147 in colorectal cancer (CRC) extracellular vesicles (EVs) and their impact on cancer-associated fibroblasts (CAFs) remains unclear.
• Previous work showed CD147 influences EV secretion in CRC stem cells (CR-CSCs) and induces invasive features in recipient cells.

Purpose of the Study:

• To investigate the role of CD147-expressing small extracellular vesicles (sEVs-CD147) in activating cancer-associated fibroblasts (CAFs) in colorectal cancer.
• To elucidate the mechanisms by which sEVs-CD147-activated CAFs influence CR-CSC invasiveness and tumor growth.
• To confirm the in vivo effects of sEV-CD147 on fibroblast activation and metabolic modulation.

Main Methods:

• Treatment of CAFs with sEVs-CD147.
• Analysis of CAF activation markers, aerobic glycolysis, and signaling pathways (β-catenin, NFκβ).
• Assessment of nitric oxide (NO) and VEGF secretion.
• In vitro co-culture assays with CR-CSCs and in vivo tumor growth studies.
• Spatial proteomics analysis of tumor tissues.

Main Results:

• sEVs-CD147 increased myofibroblast and activation markers in CAFs.
• Activated CAFs exhibited enhanced aerobic glycolysis, lactate release, NFκβ upregulation, and NO/VEGF secretion.
• Co-culture with activated CAFs promoted CR-CSC invasivity and tumor growth in vivo.
• Spatial proteomics confirmed fibroblast activation and metabolic changes in vivo.

Conclusions:

• sEV-packaged CD147 plays a crucial role in activating cancer-associated fibroblasts in colorectal cancer.
• Activated CAFs promote tumor progression by modifying stromal metabolism, involving pathways like β-catenin and NFκβ.
• Targeting the CD147-CAF axis could offer a novel therapeutic strategy for colorectal cancer.