Targeting EP2 receptor with multifaceted mechanisms for high-risk neuroblastoma
Year: 2022
Type: article
Abstract: Prostaglandin E 2 (PGE 2 ) promotes tumor cell proliferation, migration, and invasion, fostering an inflammation-enriched microenvironment that facilitates angiogenesis and immune evasion. However, the PGE 2 receptor subtype (EP1–EP4) involved in neuroblastoma (NB) growth remains elusive. Herein, we show that the EP2 receptor highly correlates with NB aggressiveness and acts as a predominant Gα s -coupled receptor mediating PGE 2 -initiated cyclic AMP (cAMP) signaling in NB cells with high-risk factors, including 11q deletion and MYCN amplification. Knockout of EP2 in NB cells blocks the development of xenografts, and its conditional knockdown prevents established tumors from progressing. Pharmacological inhibition of EP2 by our recently developed antagonist TG6-129 suppresses the growth of NB xenografts in nude mice and syngeneic allografts in immunocompetent hosts, accompanied by anti-inflammatory, antiangiogenic, and apoptotic effects. This proof-of-concept study suggests that the PGE 2 /EP2 signaling pathway contributes to NB malignancy and that EP2 inhibition by our drug-like compounds provides a promising strategy to treat this deadly pediatric cancer.
Source: Cell Reports
Authors: Ruida Hou, Ying Yu, Madison N. Sluter, Lexiao Li, Jiukuan Hao, Jie Fang, Jun Yang, Jianxiong Jiang
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: Targeting Prostaglandin Receptor EP2 for Glioma and Associated Epilepsy, Development of small molecules to target KDM4B, G4270194952, Targeting TRPC3 Channels for Epileptic Seizures, G5775726095, G6206432300, The role of JMJD6 in MYC-mediated neuroblastoma, G8321035816, The functions of JMJD6 in MYC-mediated cancer, Inflammatory regulation of epileptogenesis after status epilepticus
OpenAlex ID: W4283272265