ArticleCell communication and signaling : CCS2024
Extracellular vesicles containing MFGE8 from colorectal cancer facilitate macrophage efferocytosis.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed.
- An adhesive hydrogel enabling spatiotemporal delivery of umbilical cord exosomes for scarless skin regeneration through immunomodulation and ECM remodeling.Bioactive materials · 2027Article
- Spatial and Temporal Heterogeneity of Macrophage Efferocytosis in Tumors: Emerging Implications for Immunotherapy Biomarkers and Therapeutic Timing.Cancer medicine · 2026Review
- Exosome Secretion Drives Chemo-Resistance of Temozolomide in Glioblastoma.Journal of extracellular biology · 2026Article
- MALDI-TOF Mass Spectrometry for Glioblastoma Secretome Biomarker Screening: A Review of Challenges and Perspectives.Current issues in molecular biology · 2026Review
- Parabacteroides goldsteinii and its metabolite 7-KLCA attenuate endometriosis via TGR5 to reprogram macrophages by modulating the PPARγ/GPR132 axis.NPJ biofilms and microbiomes · 2026Article
- Review
- Article
- Vaccination of mice with Trichinella spiralis serine proteinase enhanced gut epithelial barrier and elicited a high protective immunity.PLoS neglected tropical diseases · 2026Article
- Emerging insights into exosomal protein functions in colorectal cancer.Discover oncology · 2026Review
- Multi-omics profiling identifies ADAM9 as a key efferocytosis driver in lung adenocarcinoma.Frontiers in immunology · 2026Article
- Postnatal Maxillofacial "Developing" Decellularized Extracellular Matrix Orchestrates Hierarchical Cross-Organ Regeneration via Macrophage Integrin αvβ5-Mediated Efferocytosis-Driven Developmental Recapitulation.Research (Washington, D.C.) · 2026Article
- Advancements in nanomedicine for the therapeutic regulation of efferocytosis: opportunities and challenges.Theranostics · 2026Review
- Comparative proteomic and lipidomic analysis of yak and bovine buttermilk fat globule membranes: Insights into nutritional and functional differences.Food chemistry: X · 2026Article
- MFGE8-primed fibroblasts reprogram the immunosuppressed microenvironment to promote diabetic wound healing.Frontiers in cell and developmental biology · 2026Article
- Mechanistic Insights intoEndocrine, metabolic & immune disorders drug targets · 2026Article
- Colorectal cancer-derived extracellular vesicles: at the crossroads of the tumor microenvironment and gut microbiota.Frontiers in immunology · 2026Review
- Modulating efferocytosis in the intestinal epithelial cells during colorectal cancer.Frontiers in oncology · 2026Article
- The role of extracellular vesicles in the transport and regulation of novel inflammatory mediators in IBD and its associated CRC.Frontiers in cell and developmental biology · 2026Review
- Efferocytosis in Health and Disease.MedComm · 2025Review
- Exploration of the roles of CAFs in melanoma based on single-cell transcriptomics and spatial transcriptomics.Discover oncology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundColorectal cancer (CRC) commonly exhibits tolerance to cisplatin treatment, but the underlying mechanisms remain unclear. Within the tumor microenvironment, macrophages play a role in resisting the cytotoxic effects of chemotherapy by engaging in efferocytosis to clear apoptotic cells induced by chemotherapeutic agents. The involvement of extracellular vesicles (EVs), an intercellular communicator within the tumor microenvironment, in regulating the efferocytosis for the promotion of drug resistance has not been thoroughly investigated.
methodsWe constructed GFP fluorescent-expressing CRC cell lines (including GFP-CT26 and GFP-MC38) to detect macrophage efferocytosis through flow cytometric analysis. We isolated and purified CRC-secreted EVs using a multi-step ultracentrifugation method and identified them through electron microscopy and nanoflow cytometry. Proteomic analysis was conducted to identify the protein molecules carried by CRC-EVs. MFGE8 knockout CRC cell lines were constructed using CRISPR-Cas9, and their effects were validated through in vitro and in vivo experiments using Western blotting, immunofluorescence, and flow cytometric analysis, confirming that these EVs activate the macrophage αvβ3-Src-FAK-STAT3 signaling pathway, thereby promoting efferocytosis.
resultsIn this study, we found that CRC-derived EVs (CRC-EVs) enhanced macrophage efferocytosis of cisplatin-induced apoptotic CRC cells. Analysis of The Cancer Genome Atlas (TCGA) database revealed a high expression of the efferocytosis-associated gene MFGE8 in CRC patients, suggesting a poorer prognosis. Additionally, mass spectrometry-based proteomic analysis identified a high abundance of MFGE8 protein in CRC-EVs. Utilizing CRISPR-Cas9 gene edition system, we generated MFGE8-knockout CRC cells, demonstrating that their EVs fail to upregulate macrophage efferocytosis in vitro and in vivo. Furthermore, we demonstrated that MFGE8 in CRC-EVs stimulated macrophage efferocytosis by increasing the expression of αvβ3 on the cell surface, thereby activating the intracellular Src-FAK-STAT3 signaling pathway.
conclusionsTherefore, this study highlighted a mechanism in CRC-EVs carrying MFGE8 activated the macrophage efferocytosis. This activation promoted the clearance of cisplatin-induced apoptotic CRC cells, contributing to CRC resistance against cisplatin. These findings provide novel insights into the potential synergistic application of chemotherapy drugs, EVs inhibitors, and efferocytosis antagonists for CRC treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.