ArticleNeoplasia (New York, N.Y.)2012
Genetic and pharmacologic inhibition of complement impairs endothelial cell function and ablates ovarian cancer neovascularization.
Article in Neoplasia (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 131 citations in OpenAlex.
- A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Liposomes in tumor treatment: a double-edged sword.Science China. Life sciences · 2026Review
- Understanding the role of C5a/C5aR1-mediated complement activation pathway in tumor progression and therapy resistance.Science China. Life sciences · 2026Review
- Single-cell analysis reveals the prognostic role of immune escape in the colorectal cancer microenvironment.Translational cancer research · 2026Article
- C5aR1 Inhibition Alleviates Cranial Radiation-Induced Cognitive Decline.Cancer research · 2026Article
- Review
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- A prognostic microRNA-based signature for localized clear cell renal cell carcinoma: the Bio-miR study.British journal of cancer · 2025Article
- C5a/C5aR pathway blocking promoted CuS-mediated cancer therapy effect by inhibiting cuproptosis resistance.Journal for immunotherapy of cancer · 2025Article
- The complement system and kidney cancer: pathogenesis to clinical applications.The Journal of clinical investigation · 2025Review
- Proteomic and In Silico Analyses Highlight Complement System's Role in Bladder Cancer Immune Regulation.Medicina (Kaunas, Lithuania) · 2025Article
- The role of the complement system in the response to cytotoxic therapy.Seminars in immunology · 2025Review
- Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.Gynecologic oncology · 2025Article
- The dual nature of immunotherapy in female reproductive disorders: immune homeostasis and clinical challenges.Frontiers in immunology · 2025Review
- Non-canonical extracellular complement pathways and the complosome paradigm in cancer: a scoping review.Frontiers in immunology · 2025Article
- Complement factor H in molecular regulation of angiogenesis.Medical review (2021) · 2024Review
- Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer.The Journal of clinical investigation · 2024Observational
- Blockade of C5a receptor unleashes tumor-associated macrophage antitumor response and enhances CXCL9-dependent CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Exosomal biomarkers in the differential diagnosis of ovarian tumors: the emerging roles of CA125, HE4, and C5a.Journal of ovarian research · 2024Article
- New insights about endometriosis-associated ovarian cancer: pathogenesis, risk factors, prediction and diagnosis and treatment.Frontiers in oncology · 2024Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement activation plays a critical role in controlling inflammatory responses. To assess the role of complement during ovarian cancer progression, we crossed two strains of mice with genetic complement deficiencies with transgenic mice that develop epithelial ovarian cancer (TgMISIIR-TAg). TgMISIIR-TAg mice fully or partially deficient for complement factor 3 (C3) (Tg(+)C3(KO) and Tg(+)C3(HET), respectively) or fully deficient for complement factor C5a receptor (C5aR) (Tg(+)C5aR(KO)) develop either no ovarian tumors or tumors that were small and poorly vascularized compared to wild-type littermates (Tg(+)C3(WT), Tg(+)C5aR(WT)). The percentage of tumor infiltrating immune cells in Tg(+)C3(HET) tumors compared to Tg(+)C3(WT) controls was either similar (macrophages, B cells, myeloid-derived suppressor cells), elevated (effector T cells), or decreased (regulatory T cells). Regardless of these ratios, cytokine production by immune cells taken from Tg(+)C3(HET) tumors was reduced on stimulation compared to Tg(+)C3(WT) controls. Interestingly, CD31(+) endothelial cell (EC) function in angiogenesis was significantly impaired in both C3(KO) and C5aR(KO) mice. Further, using the C5aR antagonist PMX53, tube formation of ECs was shown to be C5a-dependent, possibly through interactions with the VEGF(165) but not VEGF(121) isoform. Finally, the mouse VEGF(164) transcript was underexpressed in C3(KO) livers compare to C3(WT) livers. Thus, we conclude that complement inhibition blocks tumor outgrowth by altering EC function and VEGF(165) expression.
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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.