Opposing roles of PGD(2) in GSM

Autor(es)

Ferreira, Matthew Thomas ^[1] ; Gomes, Renata Nascimento ^[1] ; Panagopoulos, Alexandros Theodoros ^[2] ; de Almeida, Fernando Gonsalves ^[3] ; Esteves Veiga, Jose Carlos ^[2] ; Colquhoun, Alison ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil

^[2] Santa Casa Hosp, Dept Neurosurg, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, CEFAP, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Prostaglandins & Other Lipid Mediators; v. 134, p. 66-76, JAN 2018.
• Citações Web of Science: 2

Resumo

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-2 (PGD(2)) 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(2) on GBM cell activities in vitro. Methods: First we looked to identify the presence of the PGD(2) synthesis pathway through RT-PCR, immunohistochemistry, and HPLC-MS/MS in three GBM cell lines. Then, to observe PGD(2)'s effects on cell count and apoptosis/mitosis (Hoechst 33342 stain), and migration (Transweli Assay), the cells were treated in vitro with physiological (< 1 mu M) and/or supraphysiological (> 1 mu M) concentrations of PGD(2) over 72 h. HPLC-MS/MS was used to identify the lipid composition of patients with either Grade II/III gliomas or GBM. Results: We identified the presence of endogenous PGD(2) with its corresponding enzymes and receptors. Exogenous PGD(2) both increased cell count (< 1 mu M) and decreased cell count (10 mu M) 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 5 mu M PGD(2) treatments. A very significant increase of PGD(2) was seen from Grade gliomas to GBM. Conclusions: Our study demonstrates that prostaglandin D-2 possesses a dynamic, concentration-dependent effect in GBM cell activities. The increase of PGD(2) production in GBM patients suggests a pro-tumorigenic role of PGD(2) in glioma growth and invasion. Therefore, prostaglandin signaling in GEM requires further investigation to identify new targets for more effective therapies. (AU)

• Processo FAPESP: 15/08777-0 - Eicosanóides e a biologia dos gliomas: influência sobre a proliferação e migração celular e a resposta às drogas quimioterápicas
• Beneficiário: Alison Colquhoun
• Modalidade de apoio: Auxílio à Pesquisa - Regular