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Journal of Environmental Pathology, Toxicology and Oncology
Fator do impacto: 1.625 FI de cinco anos: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Imprimir: 0731-8898
ISSN On-line: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v21.i2.20
9 pages

Prostaglandins and the Regulation of Tumor Growth

David Bishop-Bailey
Department of Cardiac, Vascular and Inflammation Research, William Harvey Research Institute, Charterhouse Square, Queen Mary's University, London, UK EC1M 6BQ
Sara Calatayud
Department of Cardiac, Vascular and Inflammation Research, William Harvey Research Institute, Charterhouse Square, Queen Mary's University, London, UK EC1M 6BQ
Timothy D. Warner
Department of Cardiac, Vascular and Inflammation Research, William Harvey Research Institute, Charterhouse Square, Queen Mary's University, London, UK EC1M 6BQ
Timothy Hla
Center for Vascular Biology, UCONN Health Center; 263 Farmington Avenue, Farmington, CT 06030
Jane A. Mitchell
Unit of Critical Care Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, UK SW3 6LY

RESUMO

Increased expression of inducible cyclooxygenase (COX-2) is associated with a wide variety of tumors. In addition, inhibitors of COX have shown a great deal of promise in vitro and in animal models as potential antitumor therapies. COX enzymes use the substrate arachidonic acid to produce prostaglandin (PG)H2, the precursor to all the prostanoids. Therefore, the release of individual prostanoids depends on the abundance and functional coupling to individual PG synthase isoenzymes. Colony stimulating factors (CSFs) are also potential antitumor agents via their ability to augment the immune response. When COX-2 is expressed, the CSF, granulocyte macrophage (GM)-CSF, and granulocyte (G)-CSF are exquisitely sensitive to endogenous PGs. In addition, the ability of COX-2 to suppress GM-CSF release is mediated via traditional IP/EP prostanoid receptors linked to cAMP-dependent pathways. Therefore, inhibition of COX-2 in tumors may have the important side effect of enhancing the immune response. Recently, novel signaling pathways for PG derivatives have been discovered; in particular the PGD2 dehydration product 15-deoxy-D12,14-(15d)-PGJ2 was identified as a ligand for the nuclear receptor/transcription factor, peroxisome proliferator-activated receptor (PPAR)-g. PPARg is present at high levels in a number of tumors, and is also present in endothelial cells. 15d-PGJ2 as well as other nonprostanoid PPARg ligands are antitumor, and antiangiogenic, by dramatically inhibiting the growth of tumor cells and endothelial cells by either causing terminal differentiation, and/or by inducing apoptosis. We have recently found that, in addition to IP and EP ligands generated by COX-2, PPARg ligands similarly inhibit GM-CSF release. Effecting individual prostanoid pathways at the level of COX expression, profile of PG products produced or selective PG receptor activation may produce novel therapies, either dependent or independent of CSF release, to target cancers.


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