ArticleGynecologic oncology2017
Tissue factor-factor VIIa complex triggers protease activated receptor 2-dependent growth factor release and migration in ovarian cancer.
Article in Gynecologic oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- The unseen architects of metastasis: coagulation factors in pre-metastatic niche development.Cell communication and signaling : CCS · 2026Review
- Elevated Platelet Aggregation in Patients with Ovarian Cancer: More than Just Increased Platelet Count.Cancers · 2024Article
- Inhibitory effect of recombinant tyrosine‑sulfated madanin‑1, a thrombin inhibitor, on the behavior of MDA‑MB‑231 and SKOV3 cellsMolecular medicine reports · 2024Article
- Involvement of Protease-Activated Receptor2 Pleckstrin Homology Binding Domain in Ovarian Cancer: Expression in Fallopian Tubes and Drug Design.Biomedicines · 2024Article
- Therapeutic Targets of Monoclonal Antibodies Used in the Treatment of Cancer: Current and Emerging.Biomedicines · 2023Review
- Review
- CD142 promotes trophoblast cell migration by inhibiting BCL2-related autophagic degradation of IL-8.In vitro cellular & developmental biology. Animal · 2023Article
- Tissue factor: a neglected role in cancer biology.Journal of thrombosis and thrombolysis · 2022Review
- Therapeutic Anticoagulation Impacts MR Morphologic Recurrence Patterns in Glioblastoma-A Matched-Pair Analysis.Journal of clinical medicine · 2022Article
- Malignant tumor is the greatest risk factor for pulmonary embolism in hospitalized patients: a single-center study.Thrombosis journal · 2021Article
- Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2021Review
- Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System.International journal of molecular sciences · 2020Review
- Unintended Effects of GPCR-Targeted Drugs on the Cancer Phenotype.Trends in pharmacological sciences · 2020Review
- Prognostic significance of tissue factor in patients with pancreatic cancer: a systematic review protocol.BMJ open · 2020Article
- Article
- PRSS21/testisin inhibits ovarian tumor metastasis and antagonizes proangiogenic angiopoietins ANG2 and ANGPTL4.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2-Mediated Signaling: Co-Conspirators in Cancer Progression.Cancer research · 2019Review
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- Coagulation in Brain Tumors: Biological Basis and Clinical Implications.Frontiers in neurology · 2019Review
- GPCR Modulation in Breast Cancer.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveEnhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC.
methodsTCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines. PAR-1 and PAR-2 protein expressions were similarly examined. The PAR dependence of VEGF-A release (ELISA) and chemotactic migration in response to FVIIa and cellular proliferation in response to thrombin was evaluated with small molecule antagonists.
resultsRelative mRNA expression consistently demonstrated PAR-2>PAR-1≫PAR-3/4 in multiple EOC datasets. Human EOC cell line lysates confirmed expression of TF, PAR-1 and PAR-2 proteins. MPs isolated from EOC cell lines demonstrated markedly enhanced (4-10 fold) TF coagulant activity relative to control cell lines. FVIIa induced a dose-dependent increase in VEGF-A release (2.5-3 fold) from EOC cell lines that was abrogated by the PAR-2 antagonist ENMD-1068. FVIIa treatment of CaOV-3 and OVCAR-3 cells resulted in increased chemotactic migration that was abolished by ENMD-1068. Thrombin induced dose-dependent EOC cell line proliferation was completely reversed by the PAR-1 antagonist vorapaxar. Small molecule antagonists had no effect on these phenotypes without protease present.
conclusionsEnhanced activity of the TF-FVIIa-PAR-2 axis may contribute to the EOC progression via PAR-2 dependent signaling that supports an angiogenic and invasive phenotype and local thrombin generation supporting PAR-1 dependent proliferation.
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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.