Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma

• Published in: Molecular cancer therapeutics Vol. 7; no. 10; pp. 3420 - 3428
• Main Authors: Payne, Cathy A, Maleki, Sanaz, Messina, Marinella, O'Sullivan, Maree G, Stone, Glenn, Hall, Nathan R, Parkinson, Jonathon F, Wheeler, Helen R, Cook, Raymond J, Biggs, Michael T, Little, Nicholas S, Teo, Charles, Robinson, Bruce G, McDonald, Kerrie L
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-10-2008
• Subjects: astrocytoma; Astrocytoma - enzymology; Astrocytoma - genetics; Astrocytoma - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - pharmacology; DNA Methylation - drug effects; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immunohistochemistry; Intramolecular Oxidoreductases - deficiency; Intramolecular Oxidoreductases - genetics; Introns - genetics; Lipocalins - genetics; Multivariate Analysis; progression; Proportional Hazards Models; Prostaglandin D2 - pharmacology; prostaglandin D2 synthase; Protein Transport - drug effects; Survival Analysis
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.MCT-08-0629

Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D 2 (PGD 2 ) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system,
is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival.
In vitro , the addition of the main PGDS metabolite, PGD 2 , to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD 2 substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early
interventional efforts for the grade 2 and 3 astrocytomas. [Mol Cancer Ther 2008;7(10):3420–8]