ArticleJournal of experimental & clinical cancer research : CR2017
Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- A CD138+ tumor-associated macrophage/Siglec-F+ neutrophil feed-forward loop promotes immune evasion in pancreatic cancer.The Journal of clinical investigation · 2026Article
- Formyl peptide receptor 2 activation by MR-39 inhibits glioblastoma cell proliferation and invasiveness through suppression of multiple oncogenic pathways.Journal of translational medicine · 2026Article
- Pro-resolving lipid mediators in diseases: exploring the molecular basis and clinical implication.Molecular biomedicine · 2026Review
- Lipoxins as Modulators of Diseases.Cells · 2025Review
- A pH-sensitive peptide amphiphilic-based drug delivery system inhibits hepatocellular carcinoma growth by suppressing hepatic stellate cell activation.Materials today. Bio · 2025Article
- Immunoregulatory mechanisms of the arachidonic acid pathway in cancer.FEBS letters · 2025Review
- Use of Stromal Intervention and Exogenous Neoantigen Vaccination to Boost Pancreatic Cancer Chemo-Immunotherapy by Nanocarriers.Bioengineering (Basel, Switzerland) · 2023Article
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation.Nature reviews. Genetics · 2023Review
- The Role of Specialized Pro-Resolving Lipid Mediators in Inflammation-Induced Carcinogenesis.International journal of molecular sciences · 2023Review
- A Quick Guide to CAF Subtypes in Pancreatic Cancer.Cancers · 2023Review
- Lipid Metabolic Alterations in KRAS Mutant Tumors: Unmasking New Vulnerabilities for Cancer Therapy.International journal of molecular sciences · 2023Review
- Sildenafil Inhibits the Growth and Epithelial-to-mesenchymal Transition of Cervical Cancer via the TGF-β1/Smad2/3 Pathway.Current cancer drug targets · 2023Article
- Review
- Targeting TGF-β signal transduction for fibrosis and cancer therapy.Molecular cancer · 2022Review
- MSCs can be a double-edged sword in tumorigenesis.Frontiers in oncology · 2022Review
- Carcinogenesis: Failure of resolution of inflammation?Pharmacology & therapeutics · 2021Review
- Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis.International journal of molecular sciences · 2021Review
- Specialized Pro-Resolving Mediators Mitigate Cancer-Related Inflammation: Role of Tumor-Associated Macrophages and Therapeutic Opportunities.Frontiers in immunology · 2021Review
- Nanomedicine Strategies to Enhance Tumor Drug Penetration in Pancreatic Cancer.International journal of nanomedicine · 2021Review
- Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling.Frontiers in oncology · 2021Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPancreatic cancer is a lethal disease in part because of its potential for aggressive invasion and metastasis. Lipoxin A4 (LXA4) is one of the metabolites that is derived from arachidonic acid and that is catalyzed by 15-lipoxygenase (15-LOX), and it has recently been reported to exhibit anti-cancer effects. However, the role of LXA4 in pancreatic cancer remains to be elucidated.
methodsPancreatic cell lines were treated with vehicle or LXA4, and the invasive capacity was then assessed by Transwell assays. The expression of epithelial and mesenchymal markers was determined by western blotting and immunofluorescence. Anti-TGF-β1 neutralizing antibody and exogenous recombinant human TGF-β1 (rhTGF-β1) were used to study the effect of LXA4 on the TGF-β signaling. A liver metastasis model was applied to investigate the effect of LXA4 in vivo. The correlation between the Lipoxin effect score (LES) and the clinical-pathological features of pancreatic cancer was also analyzed.
resultsWe found that in patients with pancreatic cancer, low LES was correlated with aggressive metastatic potential. The LXA4 activity, which was mediated by the LXA4 receptor FPRL1, could significantly suppress invasion capacity and mesenchymal phenotypes. The expression and autocrine signaling pathway activity of TGF-β1 were also downregulated by LXA4. In the liver metastasis model in nude mice, the stable analog of LXA4, BML-111, could inhibit the metastasis of pancreatic cancer cells.
conclusionOur results demonstrated that LXA4 could reverse mesenchymal phenotypes, which attenuated invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer, which may provide a new strategy to prevent the metastasis of pancreatic cancer.
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