ArticleProceedings of the National Academy of Sciences of the United States of America2015
COX/mPGES-1/PGE2 pathway depicts an inflammatory-dependent high-risk neuroblastoma subset.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 102 citations in OpenAlex.
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- TFAP2D drives neuroblastoma progression: a disulfidptosis-fatty acid metabolism-based molecular subtyping and prognostic model.Translational pediatrics · 2026Article
- Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities.Journal of experimental & clinical cancer research : CR · 2025Review
- Tertiary Lymphoid Structures Are Associated with Progression-Free Survival of Peripheral Neuroblastic Tumor Patients.Cancers · 2025Article
- Aspirin Eugenol Ester Alleviates Energy Metabolism Disorders by Reducing Oxidative Damage and Inflammation in the Livers of Broilers Under High-Stocking-Density Stress.International journal of molecular sciences · 2025Article
- Pivotal roles for cancer cell-intrinsic mPGES-1 and autocrine EP4 signaling in suppressing antitumor immunity.JCI insight · 2024Article
- Targeting metabolism to enhance immunotherapy within tumor microenvironment.Acta pharmacologica Sinica · 2024Review
- Molecular profiling of core immune-escape genes highlights TNFAIP3 as an immune-related prognostic biomarker in neuroblastoma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Molecular understanding and clinical aspects of tumor-associated macrophages in the immunotherapy of renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2024Review
- Review
- High-content screening of drug combinations of an mPGES-1 inhibitor in multicellular tumor spheroids leads to mechanistic insights into neuroblastoma chemoresistance.Molecular oncology · 2024Article
- Targeting the myeloid microenvironment in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2023Review
- Neuroblastoma: an ongoing cold front for cancer immunotherapy.Journal for immunotherapy of cancer · 2023Review
- Dietary fat and lipid metabolism in the tumor microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Review
- Control of tumor-associated macrophage responses by nutrient acquisition and metabolism.Immunity · 2023Review
- The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment.Frontiers in pharmacology · 2023Article
- Targeting macrophage Syk enhances responses to immune checkpoint blockade and radiotherapy in high-risk neuroblastoma.Frontiers in immunology · 2023Article
- Prostaglandin E2 in neuroblastoma: Targeting synthesis or signaling?Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Reversing PD-1 Resistance in B16F10 Cells and Recovering Tumour Immunity Using a COX2 Inhibitor.Cancers · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The majority of solid tumors are presented with an inflammatory microenvironment. Proinflammatory lipid mediators including prostaglandin E2 (PGE2) contribute to the establishment of inflammation and have been linked to tumor growth and aggressiveness. Here we show that high-risk neuroblastoma with deletion of chromosome 11q represents an inflammatory subset of neuroblastomas. Analysis of enzymes involved in the production of proinflammatory lipid mediators showed that 11q-deleted neuroblastoma tumors express high levels of microsomal prostaglandin E synthase-1 (mPGES-1) and elevated levels of PGE2. High mPGES-1 expression also corresponded to poor survival of neuroblastoma patients. Investigation of the tumor microenvironment showed high infiltration of tumor-promoting macrophages with high expression of the M2-polarization markers CD163 and CD206. mPGES-1-expressing cells in tumors from different subtypes of neuroblastoma showed differential expression of one or several cancer-associated fibroblast markers such as vimentin, fibroblast activation protein α, α smooth muscle actin, and PDGF receptor β. Importantly, inhibition of PGE2 production with diclofenac, a nonselective COX inhibitor, resulted in reduced tumor growth in an in vivo model of 11q-deleted neuroblastoma. Collectively, these results suggest that PGE2 is involved in the tumor microenvironment of specific neuroblastoma subgroups and indicate that therapeutic strategies using existing anti-inflammatory drugs in combination with current treatment should be considered for certain neuroblastomas.
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