Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment

Glioblastoma (GBM) is the most common and aggressive form of malignant glioma. The GBM tumor microenvironment (TME) is a complex ecosystem of heterogeneous cells and signaling factors. Glioma associated macrophages and microglia (GAMs) constitute a significant portion of the TME, suggesting that the...

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Main Authors: Phillip T. Dean, Shelley B. Hooks
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1116014/full
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author Phillip T. Dean
Shelley B. Hooks
author_facet Phillip T. Dean
Shelley B. Hooks
author_sort Phillip T. Dean
collection DOAJ
description Glioblastoma (GBM) is the most common and aggressive form of malignant glioma. The GBM tumor microenvironment (TME) is a complex ecosystem of heterogeneous cells and signaling factors. Glioma associated macrophages and microglia (GAMs) constitute a significant portion of the TME, suggesting that their functional attributes play a crucial role in cancer homeostasis. In GBM, an elevated GAM population is associated with poor prognosis and therapeutic resistance. Neoplastic cells recruit these myeloid populations through release of chemoattractant factors and dysregulate their induction of inflammatory programs. GAMs become protumoral advocates through production a variety of cytokines, inflammatory mediators, and growth factors that can drive cancer proliferation, invasion, immune evasion, and angiogenesis. Among these inflammatory factors, cyclooxygenase-2 (COX-2) and its downstream product, prostaglandin E2 (PGE2), are highly enriched in GBM and their overexpression is positively correlated with poor prognosis in patients. Both tumor cells and GAMs have the ability to signal through the COX-2 PGE2 axis and respond in an autocrine/paracrine manner. In the GBM TME, enhanced signaling through the COX-2/PGE2 axis leads to pleotropic effects that impact GAM dynamics and drive tumor progression.
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spelling doaj.art-8eb1453e5a984befa61088f2580666a92023-01-26T10:26:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.11160141116014Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironmentPhillip T. DeanShelley B. HooksGlioblastoma (GBM) is the most common and aggressive form of malignant glioma. The GBM tumor microenvironment (TME) is a complex ecosystem of heterogeneous cells and signaling factors. Glioma associated macrophages and microglia (GAMs) constitute a significant portion of the TME, suggesting that their functional attributes play a crucial role in cancer homeostasis. In GBM, an elevated GAM population is associated with poor prognosis and therapeutic resistance. Neoplastic cells recruit these myeloid populations through release of chemoattractant factors and dysregulate their induction of inflammatory programs. GAMs become protumoral advocates through production a variety of cytokines, inflammatory mediators, and growth factors that can drive cancer proliferation, invasion, immune evasion, and angiogenesis. Among these inflammatory factors, cyclooxygenase-2 (COX-2) and its downstream product, prostaglandin E2 (PGE2), are highly enriched in GBM and their overexpression is positively correlated with poor prognosis in patients. Both tumor cells and GAMs have the ability to signal through the COX-2 PGE2 axis and respond in an autocrine/paracrine manner. In the GBM TME, enhanced signaling through the COX-2/PGE2 axis leads to pleotropic effects that impact GAM dynamics and drive tumor progression.https://www.frontiersin.org/articles/10.3389/fonc.2022.1116014/fullglioblastomaCOX-2PGE2microgliamacrophageinflammation
spellingShingle Phillip T. Dean
Shelley B. Hooks
Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment
Frontiers in Oncology
glioblastoma
COX-2
PGE2
microglia
macrophage
inflammation
title Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment
title_full Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment
title_fullStr Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment
title_full_unstemmed Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment
title_short Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment
title_sort pleiotropic effects of the cox 2 pge2 axis in the glioblastoma tumor microenvironment
topic glioblastoma
COX-2
PGE2
microglia
macrophage
inflammation
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1116014/full
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