Opposing roles of PGD2 in GBM

• Published in: Prostaglandins & other lipid mediators 2018-01, Vol.134, p.66-76
• Main Authors: Ferreira, Matthew Thomas, Gomes, Renata Nascimento, Panagopoulos, Alexandros Theodoros, de Almeida, Fernando Gonçalves, Veiga, José Carlos Esteves, Colquhoun, Alison
• Format: Article
• Language: English
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2017.10.002

•PGD2 possesses both pro- and anti-inflammatory effects in cancer.•PGD2 synthesis pathway was preserved in five cell lines and in GBM samples from patients, whereas patients with Grades II/III astrocytomas had significantly less PGD2.•In vitro, the cells’ growth response was contrary between nanomolar and micromolar concentrations of PGD2.•Higher levels of PGD2 decreased mitosis and increased migration. 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 D2 (PGD2) 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 PGD2 on GBM cell activities in vitro. First we looked to identify the presence of the PGD2 synthesis pathway through RT-PCR, immunohistochemistry, and HPLC–MS/MS in three GBM cell lines. Then, to observe PGD2’s effects on cell count and apoptosis/mitosis (Hoechst 33342 stain), and migration (Transwell Assay), the cells were treated in vitro with physiological (1μM) concentrations of PGD2 over 72h. HPLC–MS/MS was used to identify the lipid composition of patients with either Grade II/III gliomas or GBM. We identified the presence of endogenous PGD2 with its corresponding enzymes and receptors. Exogenous PGD2 both increased cell count (