ArticleBlood advances2021
Polyphosphate expression by cancer cell extracellular vesicles mediates binding of factor XII and contact activation.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria.The Journal of clinical investigation · 2026Article
- A Beginner's Guide to Study the Role of Extracellular Vesicles in Coagulation.Journal of extracellular biology · 2026Review
- Inorganic Polyphosphate in Hematolymphoid Malignancies: Biological Rationale and Emerging Research Gaps.Biomolecules · 2026Review
- New proteomic signature in circulating extracellular vesicles from tumor-draining and peripheral veins of patients with lung adenocarcinoma.Cancer cell international · 2026Article
- Management of cancer-associated venous thromboembolism: Perspectives on optimizing current therapeutics with a focus on factor XI inhibition.Journal of thrombosis and thrombolysis · 2025Review
- Tissue factor, factor VIII and IX in microvesicle-induced thrombosis and tumor growth of pancreatic cancer.Thrombosis journal · 2025Article
- Microfluidics-Driven Manufacturing and Multiscale Analytical Characterization of Nanoparticle-Vesicle Hybrids.Advanced healthcare materials · 2025Article
- In response to bacteria, neutrophils release extracellular vesicles capable of initiating thrombin generation through DNA-dependent and independent pathways.Journal of leukocyte biology · 2024Article
- Cryosectioning and immunofluorescence of C. elegans reveals endogenous polyphosphate in intestinal endo-lysosomal organelles.Cell reports methods · 2024Article
- Inorganic Polyphosphate Is in the Surface ofPathogens (Basel, Switzerland) · 2024Article
- The Protein Scaffolding Functions of Polyphosphate.Journal of molecular biology · 2024Review
- Importance of Non-Covalent Interactions in Yeast Cell Wall Molecular Organization.International journal of molecular sciences · 2024Review
- Factor VIIa releases phosphatidylserine-enriched extracellular vesicles from endothelial cells by activating acid sphingomyelinase.Journal of thrombosis and haemostasis : JTH · 2023Article
- Treatment of Cancer-Associated Thrombosis: Recent Advances, Unmet Needs, and Future Direction.The oncologist · 2023Article
- C1 inhibitor deficiency enhances contact pathway-mediated activation of coagulation and venous thrombosis.Blood · 2023Article
- Combined oral contraceptives may activate the contact system in healthy women.Research and practice in thrombosis and haemostasis · 2023Article
- Mechanisms of platelet activation in cancer-associated thrombosis: a focus on myeloproliferative neoplasms.Frontiers in cell and developmental biology · 2023Review
- Pathophysiology of Coagulation and Emerging Roles for Extracellular Vesicles in Coagulation Cascades and Disorders.Journal of clinical medicine · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Extracellular vesicles (EV) have been implicated in diverse biological processes, including intracellular communication, transport of nucleic acids, and regulation of vascular function. Levels of EVs are elevated in cancer, and studies suggest that EV may stimulate thrombosis in patients with cancer through expression of tissue factor. However, limited data also implicate EV in the activation of the contact pathway of coagulation through activation of factor XII (FXII) to FXIIa. To better define the ability of EV to initiate contact activation, we compared the ability of EV derived from different cancer cell lines to activate FXII. EV from all cell lines activated FXII, with those derived from pancreatic and lung cancer cell lines demonstrating the most potent activity. Concordant with the activation of FXII, EV induced the cleavage of high molecular weight kininogen (HK) to cleaved kininogen. We also observed that EVs from patients with cancer stimulated FXII activation and HK cleavage. To define the mechanisms of FXII activation by EV, EV were treated with calf intestinal alkaline phosphatase or Escherichia coli exopolyphosphatase to degrade polyphosphate; this treatment blocked binding of FXII to EVs and the ability of EV to mediate FXII activation. In vivo, EV induced pulmonary thrombosis in wild-type mice, with protection conferred by a deficiency in FXII, HK, or prekallikrein. Moreover, pretreatment of EVs with calf intestinal alkaline phosphatase inhibited their prothrombotic effect. These results indicate that polyphosphate mediates the binding of contact factors to EV and that EV-associated polyphosphate may contribute to the prothrombotic effects of EV in cancer.
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