Targeting EP2 receptor with multifaceted mechanisms for high-risk neuroblastoma.

ABSTRACT: Prostaglandin E₂ (PGE₂) promotes tumor cell proliferation, migration, and invasion, fostering an inflammation-enriched microenvironment that facilitates angiogenesis and immune evasion. However, the PGE₂ 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 PGE₂-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 devel

SUBMITTER: Hou R 

PROVIDER: S-EPMC9282716 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature