You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2015MP55-06 GALECTIN-3 IS A THERAPEUTIC TARGET FOR CASTRATION-RESISTANT PROSTATE CANCER Tomoharu Fukumori, Tsogt-Ochir Dondoo, Kei Daizumoto, Tomoya Fukawa, Yasuyo Yamamoto, Kunihisa Yamaguchi, Masayuki Takahashi, and Hiro-omi Kanayama Tomoharu FukumoriTomoharu Fukumori More articles by this author , Tsogt-Ochir DondooTsogt-Ochir Dondoo More articles by this author , Kei DaizumotoKei Daizumoto More articles by this author , Tomoya FukawaTomoya Fukawa More articles by this author , Yasuyo YamamotoYasuyo Yamamoto More articles by this author , Kunihisa YamaguchiKunihisa Yamaguchi More articles by this author , Masayuki TakahashiMasayuki Takahashi More articles by this author , and Hiro-omi KanayamaHiro-omi Kanayama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2049AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Castration-resistant prostate cancer (CRPC) has been common and CRPC-related death has been increasing. Therefore, to clarify the mechanism of tumor progression and resistance to anti-androgen drug is useful for the strategy of appropriate treatment for CRPC. Galectin-3 has been shown to be correlated with tumor progression and metastasis in a variety of cancer cells through the regulation of tumor proliferation, angiogenesis, and apoptosis. Here, we investigate the effects of galectin-3 on the tumor progression and resistance to anti-androgen drug in CRPC. METHODS Endogenous galectin-3 expression was examined by immunohistochemical analysis in human CRPC specimen, and serum galectin-3 was measured by ELISA. We generated continuous galectin-3-overexpressed LNCaP cells and galectin-3-downregulated PC-3 cells using siRNA. The invasion and migration assays in LNCaP and PC-3 cells with or without galectin-3 were performed by the xCELLigence system. Androgen receptor (AR)-dependent gene PSA expression was measured by RT-PCR in LNCaP cells with or without galectin-3 cultured in androgen-depleted media and treated for 24 hours with or without DHT (1 nM) combined with mock, enzalutamide (10 µM), and bicalutamide (10 µM). Transcriptional activity of AR were measured by luciferase reporter assay for the PSA promoter. RESULTS The CRPC highly expressed galectin-3 in both cytoplasm and nuclei, and mean concentration of human serum galectin-3 adjusted by prostate volume in CRPC was higher than that of non-malignancy control (6178 vs. 1671 pg/ml, p<0.001) and hormone-naive prostate cancer (6178 vs. 3021 pg/ml, p=0.008). Overexpression of galectin-3 in LNCaP cells promoted invasion (cell index; 0.39 vs. 0.07) and migration of tumor cells (cell index; 0.30 vs. 0.02) comparing with control LNCaP cells. Downregulation of galectin-3 in PC-3 cells suppressed invasion (cell index; 1.64 vs. 0.89) and migration (cell index; 0.84 vs. 0.42) comparing with control PC-3 cells. Galectin-3 significantly suppressed anti-androgen effect induced by enzalutamide (PSA expression ratio; 0.47 vs. 0.15, p=0.005) or bicalutamide (PSA expression ratio; 0.49 vs. 0.26, p=0.001) in LNCaP comparing with controls by activating androgen transcriptional activity of AR. CONCLUSIONS These data indicate that galectin-3 is involved in the tumor progression and anti-androgen drug resistance of CRPC by regulating invasion, migration, and transcriptional activity of AR. These results suggest that galectin-3 is one of the target molecules for future treatments in CRPC. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e675 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomoharu Fukumori More articles by this author Tsogt-Ochir Dondoo More articles by this author Kei Daizumoto More articles by this author Tomoya Fukawa More articles by this author Yasuyo Yamamoto More articles by this author Kunihisa Yamaguchi More articles by this author Masayuki Takahashi More articles by this author Hiro-omi Kanayama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...