ArticleCancer science2009
Roles of a prostaglandin E-type receptor, EP3, in upregulation of matrix metalloproteinase-9 and vascular endothelial growth factor during enhancement of tumor metastasis.
Article in Cancer science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 75 citations in OpenAlex.
- [Effects of thoracic paravertebral block on postoperative analgesia and serum level of tumor marker in lung cancer patients undergoing video-assisted thoracoscopic surgery].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2015Trial
- The Role of Prostaglandins as Major Inflammatory Mediators in Colorectal Cancer.International journal of molecular sciences · 2025Review
- COX 2-inhibitors; a thorough and updated survey into combinational therapies in cancers.Medical oncology (Northwood, London, England) · 2024Review
- Incretins and microvascular complications of diabetes: neuropathy, nephropathy, retinopathy and microangiopathy.Diabetologia · 2023Review
- Prostaglandin Pathways: Opportunities for Cancer Prevention and Therapy.Cancer research · 2022Review
- Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics.Frontiers in pharmacology · 2022Review
- Sustained Inhibition of NF-κB Activity Mitigates Retinal Vasculopathy in Diabetes.The American journal of pathology · 2021Article
- Local Anesthetics and Recurrence after Cancer Surgery-What's New? A Narrative Review.Journal of clinical medicine · 2021Review
- G Protein-Coupled receptors and heterotrimeric G proteins as cancer drivers.FEBS letters · 2020Review
- The COX-2-derived PGECell communication and signaling : CCS · 2020Article
- Article
- Illuminating the Onco-GPCRome: Novel G protein-coupled receptor-driven oncocrine networks and targets for cancer immunotherapy.The Journal of biological chemistry · 2019Review
- Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2.The Journal of clinical investigation · 2019Article
- PTGER3 induces ovary tumorigenesis and confers resistance to cisplatin therapy through up-regulation Ras-MAPK/Erk-ETS1-ELK1/CFTR1 axis.EBioMedicine · 2019Article
- Bioactive lysolipids in cancer and angiogenesis.Pharmacology & therapeutics · 2019Review
- EP3 receptor antagonist L798,106 reduces proliferation and migration of SK-BR-3 breast cancer cells.OncoTargets and therapy · 2019Article
- Inhibition of Ep3 attenuates migration and promotes apoptosis of non-small cell lung cancer cells via suppression of TGF-β/Smad signaling.Oncology letters · 2018Article
- EP3 (prostaglandin E2 receptor 3) expression is a prognostic factor for progression-free and overall survival in sporadic breast cancer.BMC cancer · 2018Article
- Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.Oncotarget · 2018Article
- High glucose-induced hyperosmolarity contributes to COX-2 expression and angiogenesis: implications for diabetic retinopathy.Cardiovascular diabetology · 2016Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclooxygenase (COX)-2 is known to correlate with poor cancer prognosis and to contribute to tumor metastasis. However, the precise mechanism of this phenomenon remains unknown. We have previously reported that host stromal prostaglandin E(2) (PGE(2))-prostaglandin E2 receptor (EP)3 signaling appears critical for tumor-associated angiogenesis and tumor growth. Here we tested whether the EP3 receptor has a critical role in tumor metastasis. Lewis lung carcinoma (LLC) cells were intravenously injected into WT mice and mice treated with the COX-2 inhibitor NS-398. The nonselective COX inhibitor aspirin reduced lung metastasis, but the COX-1 inhibitor SC560 did not. The expression of matrix metalloproteinases (MMP)-9 and vascular endothelial growth factor (VEGF)-A was suppressed in NS-398-treated mice compared with PBS-treated mice. Lungs containing LLC colonies were markedly reduced in EP3 receptor knockout (EP3(-/-)) mice compared with WT mice. The expression of MMP-9 and VEGF-A was downregulated in metastatic lungs of EP3(-/-) mice. An immunohistochemical study revealed that MMP-9-expressing endothelial cells were markedly reduced in EP3(-/-) mice compared with WT mice. When HUVEC were treated with agonists for EP1, EP2, EP3, or EP4, only the EP3 agonist enhanced MMP-9 expression. These results suggested that EP3 receptor signaling on endothelial cells is essential for the MMP-9 upregulation that enhances tumor metastasis and angiogenesis. An EP3 receptor antagonist may be useful to protect against tumor metastasis.
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