Extracellular vesicle-packaged miR-4253 secreted by cancer-associated fibroblasts facilitates cell proliferation in gastric cancer by inducing macrophage M2 polarization
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View abstract on PubMed
Summary
This summary is machine-generated.Cancer-associated fibroblasts release extracellular vesicles that promote gastric cancer growth by reprogramming macrophages. These vesicles contain miR-4253, which targets IL6R, driving M2 polarization and enhancing tumor cell proliferation.
Area Of Science
- Oncology
- Cell Biology
- Molecular Biology
Background
- Cancer-associated fibroblasts (CAFs) interact with immune cells in the tumor microenvironment.
- Extracellular vesicles (EVs) mediate communication between CAFs and macrophages, influencing tumor progression.
- The specific role of CAF-EVs in gastric cancer (GC) macrophage polarization is not fully understood.
Purpose Of The Study
- To investigate the effect of CAF-secreted EVs on macrophage polarization in gastric cancer.
- To elucidate the molecular mechanisms underlying CAF-EV mediated macrophage reprogramming.
- To assess the impact of CAF-EVs on gastric cancer cell proliferation.
Main Methods
- Macrophage polarization analysis via flow cytometry and qRT-PCR.
- Gastric cancer cell proliferation assays (CCK-8, EdU, colony formation).
- Microarray analysis, dual-luciferase reporter assays, and RNA pull-down assays to explore molecular mechanisms.
Main Results
- CAF-derived EVs were found to inhibit M1 macrophage polarization and promote M2 polarization.
- miR-4253 was upregulated in CAF-EVs, and its inhibition reversed the observed macrophage polarization.
- IL6R was identified as a direct target of miR-4253, and EVs containing miR-4253 promoted GC cell proliferation.
Conclusions
- CAF-secreted EVs package miR-4253 to drive M1-to-M2 macrophage polarization by targeting IL6R.
- This reprogramming accelerates gastric cancer cell proliferation.
- EV-encapsulated miR-4253 presents a potential therapeutic target for gastric cancer.
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