ArticleProceedings of the National Academy of Sciences of the United States of America2025
Complement C3 of tumor-derived extracellular vesicles promotes metastasis of RCC via recruitment of immunosuppressive myeloid cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Tumor-derived extracellular vesicles and genitourinary cancers: from biological mechanisms to clinical applications.Frontiers in bioengineering and biotechnology · 2025Pooled it
- Beyond the primary site: Molecular insights and clinical implications of cancer metastatic overlap between lung and urological organ cancers (Review).Molecular medicine reports · 2026Review
- Tumor-Derived Complement C3 Overexpression in STK11-Mutant Lung Adenocarcinoma Drives Tumor Growth and Immune Checkpoint Inhibitor Resistance.Cancer immunology research · 2026Article
- S100A14 in Tumor-Derived EVs Targets PIAS3 to Reprogram Astrocytes and Induce Immunosuppressive Microenvironment Promoting Brain Metastasis and Germacrone Reversal Effect.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.International journal of molecular sciences · 2026Review
- Identification of shared diagnostic biomarkers and molecular pathways between chronic kidney disease and renal cell carcinoma using transcriptomics and machine learning.Translational cancer research · 2026Article
- Immune Escape in Renal Cell Carcinoma: Latest Research and Treatment Strategies.International journal of molecular sciences · 2026Review
- Mitochondrial apoptosis gene-based pathomics for ovarian cancer prognosis.Scientific reports · 2026Article
- Contribution of tumor-derived extracellular vesicles in the establishment of the pre-metastatic niche: lessons learned from past experimentations and future directions.Clinical & experimental metastasis · 2026Review
- Cancer-associated fibroblasts as a critical driver in tumor metastasis: The mechanisms and future perspectives.iScience · 2026Review
- Targeting engulfment and cell motility 1 protein methylation attenuates M2 macrophage infiltration and boosts anti-PD-1 efficacy in colorectal cancer.Gastroenterology report · 2026Article
- Metabolic Messengers: Extracellular Vesicles as Central Mediators of Metabolic Reprogramming in Renal Cell Cancer.Biomedicines · 2026Review
- AGTRAP mediates exosome-driven communication between cancer cells and macrophages via p38 MAPK pathway to promote hepatocellular carcinoma.BBA advances · 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
- Tumor-associated neutrophils in renal cell carcinoma.Frontiers in immunology · 2026Review
- Complement system in tumor growth and metastases.British journal of cancer · 2026Review
- The CCL2-CCR2 axis in primary lung cancer and pulmonary metastasis: from molecular mechanisms to therapeutic potentials.Frontiers in immunology · 2026Review
- Extracellular vesicles as modulators of cancer metabolism and microenvironment.Extracellular vesicles and circulating nucleic acids · 2026Review
- Hypoxia-driven tumor immune escape: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Obesity-driven metabolic reprogramming and immune dysfunction in renal cancer.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Heterogeneous roles of complement C3 have been implicated in tumor metastasis and are highly context dependent. However, the underlying mechanisms linking C3 to tumor metastasis remain elusive in renal cell carcinoma (RCC). Here, we demonstrate that C3 of RCC cell-derived extracellular vesicles (EVs) contributes to metastasis via polarizing tumor-associated macrophages (TAMs) into the immunosuppressive phenotype and recruiting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, EV C3 induces the secretion of CCL2 and CXCL1 by lung macrophages and subsequently enhances TAM polarization and PMN-MDSC recruitment. Notably, targeting the CCL2/CCR2 or CXCL1/CXCR2 axis with the inhibitors RS504393 or Navarixin, respectively, effectively suppresses lung metastasis induced by RCC-derived C3 in a mouse model. Clinically, RCC patients with high expression of C3 demonstrate poor prognosis. Collectively, our findings reveal that tumor-derived EV C3 induces an immunosuppressive tumor microenvironment via TAMs, and thus promoting RCC metastasis.
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