RRC ID 72593
著者 Ueno S, Sudo T, Saya H, Sugihara E.
タイトル Pigment epithelium-derived factor promotes peritoneal dissemination of ovarian cancer through induction of immunosuppressive macrophages.
ジャーナル Commun Biol
Abstract Peritoneal dissemination of ovarian cancer (OC) correlates with poor prognosis, but the mechanisms underlying the escape of OC cells from the intraperitoneal immune system have remained unknown. We here identify pigment epithelium-derived factor (PEDF) as a promoting factor of OC dissemination, which functions through induction of CD206+ Interleukin-10 (IL-10)-producing macrophages. High PEDF gene expression in tumors is associated with poor prognosis in OC patients. Concentrations of PEDF in ascites and serum are significantly higher in OC patients than those with more benign tumors and correlated with early recurrence of OC patients, suggesting that PEDF might serve as a prognostic biomarker. Bromodomain and extraterminal (BET) inhibitors reduce PEDF expression and limit both OC cell survival and CD206+ macrophage induction in the peritoneal cavity. Our results thus implicate PEDF as a driver of OC dissemination and identify a BET protein-PEDF-IL-10 axis as a promising therapeutic target for OC.
巻・号 5(1)
ページ 904
公開日 2022-9-2
DOI 10.1038/s42003-022-03837-4
PII 10.1038/s42003-022-03837-4
PMID 36056141
PMC PMC9440245
MeSH Eye Proteins Female Humans Interleukin-10 / metabolism Macrophages / metabolism Nerve Growth Factors Ovarian Neoplasms* / metabolism Serpins* / genetics Serpins* / metabolism
IF 4.165
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)