ArticleThe Journal of biological chemistry2002
Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion.
Article in The Journal of biological chemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 260 citations in OpenAlex.
- Systematic review and meta-analysis of the benefit of celecoxib in treating advanced non-small-cell lung cancer.Drug design, development and therapy · 2018Pooled it
- Guideline
- Trial
- Role of nitric oxide, prostaglandins, thromboxanes and endothelins in lung cancer: An overview.World journal of clinical cases · 2025Review
- Review
- Lipid Metabolic Alterations in KRAS Mutant Tumors: Unmasking New Vulnerabilities for Cancer Therapy.International journal of molecular sciences · 2023Review
- The Role of Immune Modulatory Cytokines in the Tumor Microenvironments of Head and Neck Squamous Cell Carcinomas.Cancers · 2022Review
- Small Molecule Compounds of Natural Origin Target Cellular Receptors to Inhibit Cancer Development and Progression.International journal of molecular sciences · 2022Review
- Combination of EPOncoimmunology · 2021Article
- Enhanced migration of breast and lung cancer cells deficient for cN-II and CD73 via COX-2/PGE2/AKT axis regulation.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- KSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma.PLoS pathogens · 2020Article
- Tea polyphenols attenuate liver inflammation by modulating obesity-related genes and down-regulating COX-2 and iNOS expression in high fat-fed dogs.BMC veterinary research · 2020Article
- Review
- The Role of Interleukin 1β in the Pathogenesis of Lung Cancer.JTO clinical and research reports · 2020Review
- Inhibition of PI3K-AKT Signaling Blocks PGEOncoTargets and therapy · 2020Article
- Comparison of the benefits of celecoxib combined with anticancer therapy in advanced non-small cell lung cancer: A meta-analysis.Journal of Cancer · 2020Article
- HMGB1 promotes hair growth via the modulation of prostaglandin metabolism.Scientific reports · 2019Article
- Article
- Article
- Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Tumor cyclooxygenase-2 (COX-2) expression is known to be associated with enhanced tumor invasiveness. In the present study, we evaluated the importance of the COX-2 product prostaglandin E2 (PGE2) and its signaling through the EP4 receptor in mediating non-small cell lung cancer (NSCLC) invasiveness. Genetic inhibition of tumor COX-2 led to diminished matrix metalloproteinase (MMP)-2, CD44, and EP4 receptor expression and invasion. Treatment of NSCLC cells with exogenous 16,16-dimethylprostaglandin E2 significantly increased EP4 receptor, CD44, and MMP-2 expression and matrigel invasion. In contrast, anti-PGE2 decreased EP4 receptor, CD44, and MMP-2 expression in NSCLC cells. EP4 receptor signaling was found to be central to this process, because antisense oligonucleotide-mediated inhibition of tumor cell EP4 receptors significantly decreased CD44 expression. In addition, agents that increased intracellular cAMP, as is typical of EP4 receptor signaling, markedly increased CD44 expression. Moreover, MMP-2-AS treatment decreased PGE2-mediated CD44 expression, and CD44-AS treatment decreased MMP-2 expression. Thus, PGE2-mediated effects through EP4 required the parallel induction of both CD44 and MMP-2 expression because genetic inhibition of either MMP-2 or CD44 expression effectively blocked PGE2-mediated invasion in NSCLC. These findings indicate that PGE2 regulates COX-2-dependent, CD44- and MMP-2-mediated invasion in NSCLC in an autocrine/paracrine manner via EP receptor signaling. Thus, blocking PGE2 production or activity by genetic or pharmacological interventions may prove to be beneficial in chemoprevention or treatment of NSCLC.
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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.