ArticleCancer research2016
MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell-Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Immunosuppressive roles of pericytes in cancer disease: insights from a systematic review and meta-analysis.Journal of translational medicine · 2026Pooled it
- Excess Cholesterol Biosynthesis by Up-regulated HMGCS1 in Colorectal Cancer Cells Induced M2-like Tumor-Associated Macrophage Polarization via Extracellular Vesicles.Cancer research and treatment · 2026Article
- Milk fat globule-EGF factor 8 enhances the proliferation and migration of thyroid carcinoma cells through epithelial-mesenchymal transition and PI3K/AKT signaling pathway.World journal of surgical oncology · 2026Article
- The Spatiotemporal Heterogeneity of Tumor-Associated Stromal Cells: Reprogramming Plasticity to Unlock Precision Cancer Immunotherapy.Cancer communications (London, England) · 2026Review
- Tumor-Associated Pericytes: Tumorigenicity and Targeting for Cancer Therapy.Current vascular pharmacology · 2026Review
- 3,3'-Diindolylmethane blocks the dissemination of gastric cancer cells in the peritoneal cavity through the MFGE8-MAPK/ERK signaling pathway.Cancer cell international · 2025Article
- Correlation ofInternational journal of molecular sciences · 2025Article
- Bridging Inflammation and Repair: The Promise of MFG-E8 in Ischemic Stroke Therapy.International journal of molecular sciences · 2025Review
- DualNetM: an adaptive dual network framework for inferring functional-oriented markers.BMC biology · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Targeting tumor-associated macrophages: Novel insights into immunotherapy of skin cancer.Journal of advanced research · 2025Review
- The paradoxical role of stem cells in osteosarcoma: from pathogenesis to therapeutic breakthroughs.Frontiers in oncology · 2025Review
- Review
- Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment.Cell & bioscience · 2024Review
- MFG-E8 promotes M2 polarization of macrophages and is associated with poor prognosis in patients with gastric cancer.Heliyon · 2024Article
- Pericytes: jack-of-all-trades in cancer-related inflammation.Frontiers in pharmacology · 2024Review
- The Importance of M1-and M2-Polarized Macrophages in Glioma and as Potential Treatment Targets.Brain sciences · 2023Review
- Macrophage's role in solid tumors: two edges of a sword.Cancer cell international · 2023Article
- Resistin targets TAZ to promote osteogenic differentiation through PI3K/AKT/mTOR pathway.iScience · 2023Article
- Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Secretion of the powerful angiogenic factor MFG-E8 by pericytes can bypass the therapeutic effects of anti-VEGF therapy, but the mechanisms by which MFG-E8 acts are not fully understood. In this study, we investigated how this factor acts to promote the growth of melanomas that express it. We found that mouse bone marrow-derived mesenchymal stromal cells (MSC) expressed a substantial amount of MFG-E8. To assess its expression from this cell type, we implanted melanoma cells and MSC derived from wild type (WT) or MFG-E8 deficient [knockout (KO)] into mice and monitored tumor growth. Tumor growth and M2 macrophages were each attenuated in subjects coimplanted with KO-MSC compared with WT-MSC. In both xenograft tumors and clinical specimens of melanoma, we found that MFG-E8 expression was heightened near blood vessels where MSC could be found. Through in vitro assays, we confirmed that WT-MSC-conditioned medium was more potent at inducing M2 macrophage polarization, compared with KO-MSC-conditioned medium. VEGF and ET-1 expression in KO-MSC was significantly lower than in WT-MSC, correlating in vivo with reduced tumor growth and numbers of pericytes and M2 macrophages within tumors. Overall, our results suggested that MFG-E8 acts at two levels, by increasing VEGF and ET-1 expression in MSC and by enhancing M2 polarization of macrophages, to increase tumor angiogenesis. Cancer Res; 76(14); 4283-92. ©2016 AACR.
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