ArticleBlood2009
Endogenous activated protein C limits cancer cell extravasation through sphingosine-1-phosphate receptor 1-mediated vascular endothelial barrier enhancement.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 76 citations in OpenAlex.
- Exercise training improves cardiopulmonary and endothelial function in women with breast cancer: findings from the Diana-5 dietary intervention study.Internal and emergency medicine · 2016Trial
- Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer.Biomarker research · 2023Review
- Identifying key multifunctional components shared by critical cancer and normal liver pathways via SparseGMM.Cell reports methods · 2023Article
- Lactoferrin and Activated Protein C: Potential Role in Prevention of Cancer Progression and Recurrence.International journal of molecular and cellular medicine · 2023Review
- The predictive effect of immune therapy and chemotherapy under T cell-related gene prognostic index for Gastric cancer.Frontiers in cell and developmental biology · 2023Article
- Garlic-Derived Organosulfur Compounds Regulate Metabolic and Immune Pathways in Macrophages and Attenuate Intestinal Inflammation in Mice.Molecular nutrition & food research · 2022Article
- Changes in dynamics of tumor/endothelial cell adhesive interactions depending on endothelial cell growth state and elastic properties.PloS one · 2022Article
- Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies.Frontiers in oncology · 2022Review
- Non-Tumor CCAAT/Enhancer-Binding Protein Delta Potentiates Tumor Cell Extravasation and Pancreatic Cancer Metastasis Formation.Biomolecules · 2021Article
- The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium.International journal of molecular sciences · 2021Article
- Different DOACs Control Inflammation in Cardiac Ischemia-Reperfusion Differently.Circulation research · 2021Article
- Article
- TR47, a PAR1-based peptide, inhibits melanoma cell migration in vitro and metastasis in vivo.Biochemical and biophysical research communications · 2018Article
- Article
- Breaking down brain barrier breaches in cerebral malaria.The Journal of clinical investigation · 2016Article
- Targeting clotting proteins in cancer therapy - progress and challenges.Thrombosis research · 2016Review
- Functional impairment of activated protein C in breast cancer - relationship to survival outcomes.American journal of cancer research · 2016Article
- Prospective evaluation of protein C and factor VIII in prediction of cancer-associated thrombosis.Thrombosis research · 2015Article
- Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment.Oncology reports · 2015Article
- Endothelial cell protein C receptor promotes MGC803 gastric cancer cells proliferation and migration by activating ERK1/2.Medical oncology (Northwood, London, England) · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Activated protein C (APC) has both anticoagulant activity and direct cell-signaling properties. APC has been reported to promote cancer cell migration/invasion and to inhibit apoptosis and therefore may exacerbate metastasis. Opposing these activities, APC signaling protects the vascular endothelial barrier through sphingosine-1-phosphate receptor-1 (S(1)P(1))activation, which may counteract cancer cell extravasation. Here, we provide evidence that endogenous APC limits cancer cell extravasation, with in vivo use of monoclonal antibodies against APC. The protective effect of endogenous APC depends on its signaling properties. The MAPC1591 antibody that only blocks anticoagulant activity of APC does not affect cancer cell extravasation as opposed to MPC1609 that blocks anticoagulant and signaling properties of APC. Combined administration of anti-APC antibodies and S(1)P(1) agonist (SEW2871) resulted in a similar number of pulmonary foci in mice in presence and absence of APC, indicating that the protective effect of APC depends on the S(1)P(1) pathway. Moreover, endogenous APC prevents cancer cell-induced vascular leakage as assessed by the Evans Blue Dye assay, and SEW2871 treatment reversed MPC1609-dependent vascular leakage. Finally, we show that cancer cells combined with MPC1609 treatment diminished endothelial VE-cadherin expression. In conclusion, endogenous APC limits cancer cell extravasation because of S(1)P(1)-mediated VE-cadherin-dependent vascular barrier enhancement.
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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.