MP90-15 GALECTIN-3 IS IMPLICATED IN THE PROGRESSION OF CASTRATION-RESISTANT PROSTATE CANCER THROUGH THE REGULATION OF ANGIOGENESIS AND ANDROGEN RECEPTOR SIGNALING

Field: Medicine (Health Sciences)

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP90-15 GALECTIN-3 IS IMPLICATED IN THE PROGRESSION OF CASTRATION-RESISTANT PROSTATE CANCER THROUGH THE REGULATION OF ANGIOGENESIS AND ANDROGEN RECEPTOR SIGNALING Tomoharu Fukumori, Kei Daizumoto, Dondoo Tsogt-Ochir, Yasuyo Yamamoto, Kunihisa Yamaguchi, Masayuki Takahashi, and Hiro-omi Kanayama Tomoharu FukumoriTomoharu Fukumori More articles by this author , Kei DaizumotoKei Daizumoto More articles by this author , Dondoo Tsogt-OchirDondoo Tsogt-Ochir 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.2016.02.2559AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Castration-resistant prostate cancer (CRPC) has been common and is the leading cause of prostate cancer death at present. Therefore, to clarify the mechanism of resistance to hormone therapy is useful for the new strategy of 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 cell proliferation, invasion, angiogenesis, and apoptosis. Here, we investigate the effects and mechanisms of galectin-3 on the tumor progression and hormone resistance for CRPC. METHODS Androgen receptor (AR)-dependent LNCaP and galectin-3-expressing LNCaP cells were cultured with androgen-depleted media with 5% charcoal-stripped serum (CSS). Cells were treated for 24 hours with or without DHT (1 nM) combined with mock, MDV3100 (10 µM), and bicalutamide (10 µM). We analyzed gene profile using microarray analysis. We also examined the tumor size, expression of CD31 and microvessel density (MVD) in the xenograft tumors of LNCaP cells with or without galectin-3 before and after castration in mice model. RESULTS Galectin-3 significantly suppressed anti-androgen effect induced by enzalutamide or bicalutamide in LNCaP comparing with controls by activating androgen transcriptional activity of AR. In microarray analysis, galectin-3 significantly upregulated expression of VEGF-B and TMPRSS2 which was located downstream of the AR. Galectin-3-null LNCaP xenograft tumors which size was at least 200 mm3 were significantly shrinking after a week from the castration. In contrast, galectin-3-expressing LNCaP xenografts were increased progressively even after castration. Immunohistochemically staining of CD31 in LNCaP xenograft tumors showed that galecitn-3-expressing LNCaP enhanced MDV (164±49.5 vs 98±29.5, p=0.026) comparing with control LNCaP cells, suggesting the important roles of galectin-3 for angiogenesis of prostate cancer cells. CONCLUSIONS The results indicate that galectin-3 is involved in the tumor progression and hormone resistance of CRPC by regulating angiogenesis and transcriptional activity of AR. These results suggest that galectin-3 is one of the target molecules for future treatments in CRPC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1150 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Tomoharu Fukumori More articles by this author Kei Daizumoto More articles by this author Dondoo Tsogt-Ochir 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 ...