TY - JOUR
T1 - Pigment epithelium-derived factor promotes peritoneal dissemination of ovarian cancer through induction of immunosuppressive macrophages
AU - Ueno, Sayaka
AU - Sudo, Tamotsu
AU - Saya, Hideyuki
AU - Sugihara, Eiji
N1 - Funding Information:
We thank T. Kitamura for providing the vectors pMXs-IRES-puro and pMXs-IRES-GFP as well as Plat-E cells; K.F. Roby for providing ID8 cells; D. Yu for providing SKOV3ip1 cells; I. Ishimatsu, S. Hayashi, and K. Sonoda for technical assistance; M. Sato and M. Kobori for help with preparation of the manuscript. This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI grant JP19K24054 (to S.U.) and by a Grant-in Aid for JSPS Fellows (to SU).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85137166948&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85137166948&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-03837-4
DO - 10.1038/s42003-022-03837-4
M3 - Article
C2 - 36056141
AN - SCOPUS:85137166948
SN - 2399-3642
VL - 5
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 904
ER -