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Opposing roles of PGD 2 in GBM.

Authors :: Ferreira MT
Gomes RN
Panagopoulos AT
de Almeida FG
Veiga JCE
Colquhoun A
Source :: Prostaglandins & other lipid mediators [Prostaglandins Other Lipid Mediat] 2018 Jan; Vol. 134, pp. 66-76. Date of Electronic Publication: 2017 Oct 16.
Publication Year :: 2018
Abstract: Background: The World Health Organization classifies glioblastoma (GBM) as a grade IV astrocytoma. Despite the advances in chemotherapy, surgery, and radiation treatments that improve a patient's length of survival, the overall trajectory of the disease remains unchanged. GBM cells produce significant levels of various types of bioactive lipids. Prostaglandin D <subscript>2</subscript> (PGD <subscript>2</subscript> ) influences both pro- and anti-tumorigenic activities in the cell; however, its role in GBM is unclear. Therefore, this study aimed to identify the impact of PGD <subscript>2</subscript> on GBM cell activities in vitro.<br />Methods: First we looked to identify the presence of the PGD <subscript>2</subscript> synthesis pathway through RT-PCR, immunohistochemistry, and HPLC-MS/MS in three GBM cell lines. Then, to observe PGD <subscript>2</subscript> 's effects on cell count and apoptosis/mitosis (Hoechst 33342 stain), and migration (Transwell Assay), the cells were treated in vitro with physiological (<1μM) and/or supraphysiological (>1μM) concentrations of PGD <subscript>2</subscript> over 72h. HPLC-MS/MS was used to identify the lipid composition of patients with either Grade II/III gliomas or GBM.<br />Results: We identified the presence of endogenous PGD <subscript>2</subscript> with its corresponding enzymes and receptors. Exogenous PGD <subscript>2</subscript> both increased cell count (<1μM) and decreased cell count (10μM) in a concentration-dependent manner. There were no significant effects on apoptosis. A significant decrease in mitotic activity was seen only in U251MG, and a significant increase was seen in migration with 5μM PGD <subscript>2</subscript> treatments. A very significant increase of PGD <subscript>2</subscript> was seen from Grade II/III gliomas to GBM.<br />Conclusions: Our study demonstrates that prostaglandin D <subscript>2</subscript> possesses a dynamic, concentration-dependent effect in GBM cell activities. The increase of PGD <subscript>2</subscript> production in GBM patients suggests a pro-tumorigenic role of PGD <subscript>2</subscript> in glioma growth and invasion. Therefore, prostaglandin signaling in GBM requires further investigation to identify new targets for more effective therapies.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)