ArticleBlood advances2021
Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles.
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 52 papers.
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Who cites it
52 citing papers in PubMed, 73 citations in OpenAlex.
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Cancer-associated arterial thromboembolism: real-world burden from a nationwide electronic health record database.Journal of the National Cancer Institute · 2026Article
- Mechanobiology of cancer-associated thrombosis: from molecular mechanisms to therapeutic innovation.Journal of nanobiotechnology · 2026Review
- Small and medium/large glioblastoma extracellular vesicles differentially regulate endothelial and mitochondrial function in blood-brain barrier and peripheral vasculature models.Journal of neuro-oncology · 2026Article
- Glioblastoma Cells Expressing Oncogenic EGFR Release Multiple Extracellular Vesicle Subpopulations Positive or Negative for EGFR.Journal of extracellular biology · 2026Article
- Exploring the dual role of extracellular vesicles in coagulation and immune modulation in glioblastoma.Scientific reports · 2026Article
- Tissue factor and regenerative medicine: shaping cell and extracellular vesicle-based therapeutic approaches.Frontiers in cell and developmental biology · 2026Review
- Clinical relevance of extracellular vesicles in cancer - therapeutic and diagnostic potential.Nature reviews. Clinical oncology · 2025Review
- Spatial transcriptomics of glioblastoma defines biologically and clinically significant reprogramming patterns across unique spatial microenvironments.bioRxiv : the preprint server for biology · 2025Article
- Article
- Evaluation of the podoplanin/C-type lectin-like receptor-2 (CLEC-2) pathway as a mediator of platelet and coagulation activation in sickle cell disease.Research and practice in thrombosis and haemostasis · 2025Article
- Biogenesis and functional implications of extracellular vesicles in cancer metastasis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- The Role of Extracellular Vesicles in the Control of Vascular Checkpoints for Cancer Metastasis.Cancers · 2025Review
- Venous Thromboembolism in Patients with Glioblastoma: Molecular Mechanisms and Clinical Implications.Thrombosis and haemostasis · 2025Review
- Article
- Glioblastoma Cells Express and Secrete Alternatively Spliced Transcripts of Coagulation Factor X.Biomedicines · 2025Article
- Podoplanin and microthrombi in lung injury.Blood vessels, thrombosis & hemostasis · 2025Article
- Role of Podoplanin (PDPN) in Advancing the Progression and Metastasis of Glioblastoma Multiforme (GBM).Cancers · 2024Review
- Cancer progression and tumor hypercoagulability: a platelet perspective.Journal of thrombosis and thrombolysis · 2024Review
- The regulation of cancer-associated thrombosis by podoplanin.Thrombosis update · 2024Article
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 3 countries.
Funding
Abstract
Vascular anomalies, including local and peripheral thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of deregulation of the cancer cell genome and epigenome. Although the molecular effectors of these changes are poorly understood, the upregulation of podoplanin (PDPN) by cancer cells has recently been linked to an increased risk for venous thromboembolism (VTE) in GBM patients. Therefore, regulation of this platelet-activating protein by transforming events in cancer cells is of considerable interest. We used single-cell and bulk transcriptome data mining, as well as cellular and xenograft models in mice, to analyze the nature of cells expressing PDPN, as well as their impact on the activation of the coagulation system and platelets. We report that PDPN is expressed by distinct (mesenchymal) GBM cell subpopulations and downregulated by oncogenic mutations of EGFR and IDH1 genes, along with changes in chromatin modifications (enhancer of zeste homolog 2) and DNA methylation. Glioma cells exteriorize their PDPN and/or tissue factor (TF) as cargo of exosome-like extracellular vesicles (EVs) shed from cells in vitro and in vivo. Injection of glioma-derived podoplanin carrying extracelluar vesicles (PDPN-EVs) activates platelets, whereas tissue factor carrying extracellular vesicles (TF-EVs) activate the clotting cascade. Similarly, an increase in platelet activation (platelet factor 4) or coagulation (D-dimer) markers occurs in mice harboring the corresponding glioma xenografts expressing PDPN or TF, respectively. Coexpression of PDPN and TF by GBM cells cooperatively affects tumor microthrombosis. Thus, in GBM, distinct cellular subsets drive multiple facets of cancer-associated thrombosis and may represent targets for phenotype- and cell type-based diagnosis and antithrombotic intervention.
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