Abstract
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.
Highlights
Glioblastoma multiforme (GBM) is a devastating disease with a bleak survival outlook of just 15 months
In a larger cohort of astrocytic tumors, we report the loss of PGDS mRNA and protein expression in malignant astrocytomas but not in AII
The expression of PGDS in the AIII and the GBM specimens were significantly reduced when compared with normal brain and AII, where levels were 2.5 and 5 times lower, respectively (P = 0.013; Fig. 1B)
Summary
Glioblastoma multiforme (GBM) is a devastating disease with a bleak survival outlook of just 15 months. GBM typically arise de novo; around 10% of these tumors arise from earlier clinical diagnoses of WHO malignancy grade 2 (AII) and grade 3 (AIII; anaplastic) astrocytoma. Patients diagnosed with an AII have an average survival of 2 to 8 years compared with 2 years for a AIII [1]. Other studies have shown no such correlation [4] Several genes such as TP53 (5 – 7), epidermal growth factor receptor [8, 9], and platelet-derived growth factor receptor [10] have been associated with the tumorigenesis and anaplastic progression of human gliomas, but the prognostic significance of these genes has been unclear. Some studies have found that TP53 mutations only predict a shorter time interval before progression in patients with AII lesions [1]
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