ArticleThe Journal of biological chemistry2013
Thrombin-cleaved fragments of osteopontin are overexpressed in malignant glial tumors and provide a molecular niche with survival advantage.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Osteopontin in Atrial Fibrillation and Atrial Remodeling.Journal of the American Heart Association · 2026Review
- The immune duality of osteopontin and its therapeutic implications for kidney transplantation.Frontiers in immunology · 2025Review
- Cerebrospinal Fluid Liquid Biopsies in the Evaluation of Adult Gliomas.Current oncology reports · 2024Review
- 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
- Osteopontin as a Biomarker in Chronic Kidney Disease.Biomedicines · 2023Review
- Assessment and prediction of glioblastoma therapy response: challenges and opportunities.Brain : a journal of neurology · 2023Article
- Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology.Biomolecules · 2023Review
- Clinical and Molecular Implications of Osteopontin in Heart Failure.Current issues in molecular biology · 2022Review
- Thrombin cleavage of osteopontin initiates osteopontin's tumor-promoting activity.Journal of thrombosis and haemostasis : JTH · 2022Article
- Development of outcome measures according to dystrophic phenotypes in canine X-linked muscular dystrophy in Japan.Experimental animals · 2021Article
- Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases.Biomedicines · 2021Review
- Article
- Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice.Frontiers in cell and developmental biology · 2021Article
- Cerebrospinal fluid biomarkers for brain tumor detection: clinical roles and current progress.American journal of translational research · 2020Review
- Osteopontin attenuates early brain injury through regulating autophagy-apoptosis interaction after subarachnoid hemorrhage in rats.CNS neuroscience & therapeutics · 2019Article
- Review
- Thrombin cleavage of osteopontin controls activation of hepatic stellate cells and is essential for liver fibrogenesis.Journal of cellular physiology · 2019Article
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Osteopontin (OPN), which is highly expressed in malignant glioblastoma (GBM), possesses inflammatory activity modulated by proteolytic cleavage by thrombin and plasma carboxypeptidase B2 (CPB2) at a highly conserved cleavage site. Full-length OPN (OPN-FL) was elevated in cerebrospinal fluid (CSF) samples from all cancer patients compared with noncancer patients. However, thrombin-cleaved OPN (OPN-R) and thrombin/CPB2-double-cleaved OPN (OPN-L) levels were markedly increased in GBM and non-GBM gliomas compared with systemic cancer and noncancer patients. Cleaved OPN constituted ∼23 and ∼31% of the total OPN in the GBM and non-GBM CSF samples, respectively. OPN-R was also elevated in GBM tissues. Thrombin-antithrombin levels were highly correlated with cleaved OPN, but not OPN-FL, suggesting that the cleaved OPN fragments resulted from increased thrombin and CPB2 in this extracellular compartment. Levels of VEGF and CCL4 were increased in CSF of GBM and correlated with the levels of cleaved OPN. GBM cell lines were more adherent to OPN-R and OPN-L than OPN-FL. Adhesion to OPN altered gene expression, in particular genes involved with cellular processes, cell cycle regulation, death, and inflammation. OPN and its cleaved forms promoted motility of U-87 MG cells and conferred resistance to apoptosis. Although functional mutation of the RGD motif in OPN largely abolished these functions, OPN(RAA)-R regained significant cell binding and signaling function, suggesting that the SVVYGLR motif in OPN-R may substitute for the RGD motif if the latter becomes inaccessible. OPN cleavage contributes to GBM development by allowing more cells to bind in niches where they acquire anti-apoptotic properties.
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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.