Cyclooxygenase-2 in glioblastoma multiforme

Abstract

Glioblastoma multiforme (GBM) represents the most prevalent brain primary tumor, yet there is a lack of effective treatment. With current therapies, fewer than 5% of patients with GBM survive more than 5 years after diagnosis. Mounting evidence from epidemiological studies reveals that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is correlated with reduced incidence of GBM, suggesting that cyclooxygenase-2 (COX-2) and its major product within the brain, prostaglandin E2 (PGE2), are involved in the development and progression of GBM. Here, we highlight our current understanding of COX-2 in GBM proliferation, apoptosis, invasion, angiogenesis, and immunosuppression by focusing on recent in vitro and in vivo experimental data. We also discuss the feasibility of COX-2 as a therapeutic target for GBM in light of the latest human studies.

Prostaglandin E2 Signaling: Alternative Target for Glioblastoma?

“…For instance, the induction of COX-2 has been widely reported in most human glioblastomas and proposed as a major factor promoting tumor development. However, the prospect of COX-2 as a therapeutic target for GBM has been dampened by recent inconsistent outcomes from a number of population studies and the early termination of several clinical trials [3]. These differing results are not unexpected, given that five prostanoid products of COX-2 activate a total of nine G protein-coupled receptors (GPCRs) to regulate a myriad of pro- and anti-inflammatory consequences [4].…”

S1P d20:1, an endogenous modulator of S1P d18:1/S1P2‐dependent signaling

“…Importantly, S1P has been shown to be upregulated in glioblastoma while the sphingosine kinase 1‐S1P 2 axis mediates glioma cell migration . Moreover, COX‐2 has been shown to be involved in the pathophysiology of glioblastoma . Thus, it is tempting to speculate that the dose‐dependent induction of COX‐2 by S1P d18:1 might contribute to glioma invasiveness.…”

A systems-based map of human brain cell-type enriched genes and malignancy-associated endothelial changes

“…TBXA2R and PTGIR encode for prostaglandin receptors, which bind thromboxane A2 and prostacyclin, respectively, products of the short lived intermediate molecule prostaglandin H 2 , generated from arachidonic acid, via cyclooxygenase (COX)-1 or −2. Several studies have demonstrated that COX-2 is elevated in GBM, and levels positively correlated with tumour grade, reoccurrence and shorter survival (Qiu et al, 2017), however, the expression of prostaglandin receptors on GBM EC, and the functional consequences, have not been explored. A panel of GBM EC-enriched genes we identified are linked through the renin-angiotensin system (RAS): angiotensin I converting enzyme (ACE), glutamyl aminopeptidase (ENPEP) and NADPH oxidase 4 (NOX4).…”