ArticleThe American journal of pathology2001
Differential expression of protease-activated receptors-1 and -2 in stromal fibroblasts of normal, benign, and malignant human tissues.
Article in The American journal of pathology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Expression of proteinase-activated receptor 1-4 (PAR 1-4) in human cancer.Journal of molecular histology · 2010Pooled it
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 2026Review
- Role of Mast Cells and Their Mediators in Chronic Kidney Diseases.International journal of molecular sciences · 2025Review
- Differential Contributions of Fibroblast Subpopulations to Intercellular Communication in Eosinophilic Esophagitis.Biology · 2024Article
- Protease activated receptor 2 as a novel druggable target for the treatment of metabolic dysfunction-associated fatty liver disease and cancer.Frontiers in immunology · 2024Review
- The effects of coagulation factors and their inhibitors on proliferation and migration in colorectal cancer.Cancer medicine · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Tie2-mediated vascular remodeling by ferritin-based protein C nanoparticles confers antitumor and anti-metastatic activities.Journal of hematology & oncology · 2020Article
- Breast cancer stromal clotting activation (Tissue Factor and thrombin): A pre-invasive phenomena that is prognostic in invasion.Cancer medicine · 2020Article
- Biomarkers and the role of mast cells as facilitators of inflammation and fibrosis in chronic kidney disease.Translational andrology and urology · 2019Review
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- Potential importance of protease activated receptor (PAR)-1 expression in the tumor stroma of non-small-cell lung cancer.BMC cancer · 2017Article
- Teleocidin A2 inhibits human proteinase-activated receptor 2 signaling in tumor cells.Pharmacology research & perspectives · 2016Article
- Protease-activated receptors (PARs)--biology and role in cancer invasion and metastasis.Cancer metastasis reviews · 2015Review
- Protease-activated receptors in the Achilles tendon-a potential explanation for the excessive pain signalling in tendinopathy.Molecular pain · 2015Article
- Activation of protease-activated receptors (PARs)-1 and -2 promotes alpha-smooth muscle actin expression and release of cytokines from human lung fibroblasts.Physiological reports · 2015Article
- Evaluation on potential contributions of protease activated receptors related mediators in allergic inflammation.Mediators of inflammation · 2014Review
- Characterization of PAR1 and FGFR1 expression in invasive breast carcinomas: Prognostic significance.Oncology letters · 2012Article
- PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis.Cancer research · 2011Review
- Protease-activated receptors in cancer: A systematic review.Oncology letters · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine proteases thrombin and trypsin are among many factors that malignant cells secrete into the extracellular space to mediate metastatic processes such as cellular invasion, extracellular matrix degradation, angiogenesis, and tissue remodeling. The degree of protease secretion from malignant cells has been correlated to their metastatic potential. Protease activated receptors (PAR)-1 and -2, which are activated by thrombin and trypsin respectively, have not been extensively characterized in human tumors in situ. We investigated the presence of PAR-1 and PAR-2 in human normal, benign and malignant tissues using immunohistochemistry and in situ hybridization. Our results demonstrate PAR-1 and PAR-2 expression in the tumor cells, mast cells, macrophages, endothelial cells, and vascular smooth muscle cells of the metastatic tumor microenvironment. Most notably, an up-regulation of PAR-1 and PAR-2 observed in proliferating, smooth muscle actin (SMA)-positive stromal fibroblasts surrounding the carcinoma cells was not observed in normal or benign conditions. Furthermore, in vitro studies using proliferating, SMA-positive, human dermal fibroblasts, and scrape-wounded human dermal fibroblasts demonstrated the presence of PAR-1 and PAR-2 not detected in quiescent, SMA-negative cultures. PAR-1 and PAR-2 in the cells forming the tumor microenvironment suggest that these receptors mediate the signaling of secreted thrombin and trypsin in the processes of cellular metastasis.
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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.