Mp69-11 Androgen Receptor Signaling Induces Angiogenesis in Irradiated Bladder Cells

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP69)1 May 2024MP69-11 ANDROGEN RECEPTOR SIGNALING INDUCES ANGIOGENESIS IN IRRADIATED BLADDER CELLS Takahiro Komori, Hiroki Ide, Fukada Junichi, Kazuhiro Matsumoto, Yuto Baba, Akari Komatsuda, Sotaro Kitaoka, Chugo Nishimura, Mototsugu Oya, and Hiroshi Miyamoto Takahiro KomoriTakahiro Komori , Hiroki IdeHiroki Ide , Fukada JunichiFukada Junichi , Kazuhiro MatsumotoKazuhiro Matsumoto , Yuto BabaYuto Baba , Akari KomatsudaAkari Komatsuda , Sotaro KitaokaSotaro Kitaoka , Chugo NishimuraChugo Nishimura , Mototsugu OyaMototsugu Oya , and Hiroshi MiyamotoHiroshi Miyamoto View All Author Informationhttps://doi.org/10.1097/01.JU.0001008892.86171.de.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The mechanism of radiation cystitis (RC) remains unknown, however, angiogenesis induced by hypoxia is important because hyperbaric oxygen therapy is clinically effective for RC. Recent studies have shown that bladder urothelium expresses androgen receptor (AR) whose signaling is involved in angiogenesis. We therefore assessed the impact of androgen deprivation therapy (ADT) on the prevention of bladder hemorrhage in men undergoing external beam radiation therapy (EBRT) for their prostate cancer (PC) and explored the association between AR signaling and angiogenesis in irradiated bladder cells. METHODS: We analyzed potential risk factors of RC, including techniques [conventional EBRT (n=135) or intensity-modulated radiation therapy (IMRT) (n=372)], ADT through the peri-radiotherapy period for at least 6 months, and clinico-pathological parameters, in a total of 507 PC patients undergoing EBRT (mean dose±SD: 78.0±4.3 Gy) at our institution and Keio University Hospital. Next, in three AR-positive bladder cancer lines (UMUC3, 5637-AR, and 647V-AR) treated with dihydrotestosterone (DHT), hydroxyflutamide (HF), or both for 48 hours and subsequently irradiated (2 Gy), we compared the expression levels of vascular endothelial growth factor receptor (VEGFR) genes (FLT1 and KDR) by a quantitative PCR method. Finally, we compared the incidence rates of gross hematuria (GH), microvessel density (MVD) and VEGFR expression of bladders between RC model mice (20 Gy) receiving sham surgery and castration. RESULTS: Of 507 PC patients undergoing EBRT, 27 with ADT versus 49 without ADT through the peri-radiotherapy period presented with GH during follow-up (mean: 102.0±36.7 months) (p=0.001). The 10-year incidence rates of GH were 15.2% and 24.1% in those with and without ADT, respectively (p=0.036). Multivariate analysis by Cox regression model revealed that the absence of ADT (HR=2.02; p=0.006) was an independent risk factor for GH. The levels of FLT1 and KDR expression were significantly higher in irradiated bladder cancer cells pretreated with DHT than in those with mock treatment. Furthermore, the effect of DHT on FLT1/KDR expression was abolished by an anti-androgen HF. Finally, the incidence rate of GH in RC model mice receiving castration was significantly lower than that in those receiving sham surgery. Correspondingly, MVD and VEGFR expression of bladders in those receiving castration were significantly lower than that in those receiving sham surgery. CONCLUSIONS: ADT through the peri-radiotherapy period has a potential for preventing RC. Our results suggest that AR activation contributes to inducing angiogenesis in irradiated bladder cells. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1123 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Takahiro Komori More articles by this author Hiroki Ide More articles by this author Fukada Junichi More articles by this author Kazuhiro Matsumoto More articles by this author Yuto Baba More articles by this author Akari Komatsuda More articles by this author Sotaro Kitaoka More articles by this author Chugo Nishimura More articles by this author Mototsugu Oya More articles by this author Hiroshi Miyamoto More articles by this author Expand All Advertisement PDF downloadLoading ...