ArticleJournal of thrombosis and haemostasis : JTH2022
Thrombin cleavage of osteopontin initiates osteopontin's tumor-promoting activity.
Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Towards an emerging role for anticoagulants in cancer therapy: a systematic review and meta-analysis.Frontiers in oral health · 2024Pooled it
- Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026Review
- Urinary thrombin as a non-invasive biomarker in renal diseases: a possible role in the detection of segmental sclerosis lesions in IgA nephropathy.Clinical and experimental nephrology · 2026Article
- Research progress on the correlation between OPN and immune escape of gastric cancer.Clinical and experimental medicine · 2026Review
- Emerging roles of haemostatic proteins as markers of disease progression and prognosis in breast cancer.Exploration of targeted anti-tumor therapy · 2026Review
- The Multifaceted Role of Osteopontin in Modulating the Tumor Microenvironment.Cancer research · 2025Review
- Role of osteopontin in cancer: From pathogenesis to therapeutics (Review).Oncology reports · 2025Review
- Small Integrin binding Ligand N-linked Glycoproteins, prostate-specific antigen and time to prostate cancer diagnosis.Matrix biology plus · 2025Article
- The immune duality of osteopontin and its therapeutic implications for kidney transplantation.Frontiers in immunology · 2025Review
- Identification of diagnostic biomarkers and immune cell infiltration in tongue squamous cell carcinoma using bioinformatic approaches.European journal of medical research · 2024Article
- Regulating protein corona on nanovesicles by glycosylated polyhydroxy polymer modification for efficient drug delivery.Nature communications · 2024Article
- Methods to Investigate Thrombin Cleavage of Osteopontin (OPN).Methods in molecular biology (Clifton, N.J.) · 2024Article
- Preliminary Study of the Relationship between Osteopontin and Relapsed Hodgkin's Lymphoma.Biomedicines · 2023Article
- Review
- Article
- The Intracellular and Secreted Sides of Osteopontin and Their Putative Physiopathological Roles.International journal of molecular sciences · 2023Review
- Article
- The Role of Osteopontin in Tumor Progression Through Tumor-Associated Macrophages.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundOsteopontin (OPN) is a multifunctional proinflammatory matricellular protein overexpressed in multiple human cancers and associated with tumor progression and metastases. Thrombin cleavage of OPN reveals a cryptic binding site for α
methodsThrombin cleavage-resistant OPN
resultsOPN-KI mice engineered with a thrombin cleavage-resistant OPN had reduced B16 melanoma growth and fewer pulmonary metastases than WT mice. The tumor suppression phenotype of the OPN-KI mouse was identical to that observed in OPN-KO mice and was replicated in WT mice by pharmacologic inhibition of thrombin with dabigatran. Tumors isolated from OPN-KI mice had increased tumor-associated macrophages with an altered activation phenotype. Immunodeficient OPN-KI mice (NOG-OPN-KI) or macrophage-depleted OPN-KI mice did not exhibit the tumor suppression phenotype. As B16 cells do not express OPN, thrombin-cleaved fragments of host OPN suppress host antitumor immune response by functionally modulating the tumor-associated macrophages. YUMM3.1 cells, which express OPN, showed less tumor suppression in the OPN-KI and OPN-KO mice than B16 cells, but its growth was suppressed by dabigatran similar to B16 cells.
conclusionsThrombin cleavage of OPN, derived from the host and the tumor, initiates OPN's tumor-promoting activity in vivo.
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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.