2. Academic Validation
  3. Pigment epithelium-derived factor promotes peritoneal dissemination of ovarian cancer through induction of immunosuppressive macrophages

Pigment epithelium-derived factor promotes peritoneal dissemination of ovarian cancer through induction of immunosuppressive macrophages

  • Commun Biol. 2022 Sep 2;5(1):904. doi: 10.1038/s42003-022-03837-4.
Sayaka Ueno 1 2,  Tamotsu Sudo 2,  Hideyuki Saya 3 4,  Eiji Sugihara 5 6
Affiliations

Affiliations

  • 1 Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
  • 2 Section of Translational Research, Hyogo Cancer Center, Hyogo, Japan.
  • 3 Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. [email protected].
  • 4 Division of Gene Regulation, Cancer Center, Research Promotion Headquarters, Fujita Health University School of Medicine, Aichi, Japan. [email protected].
  • 5 Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. [email protected].
  • 6 Division of Gene Regulation, Cancer Center, Research Promotion Headquarters, Fujita Health University School of Medicine, Aichi, Japan. [email protected].
PMID: 36056141 DOI: 10.1038/s42003-022-03837-4
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.

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