MP29-02 INCREASED EXPRESSION OF ARYL HYDROCARBON RECEPTOR IN CLEAR CELL RENAL CELL CARCINOMA AND INFILTRATING LYMPHOCYTES: IMPLICATIONS FOR CANCER INVASION, PROGNOSIS AND TUMOR IMMUNITY

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2014MP29-02 INCREASED EXPRESSION OF ARYL HYDROCARBON RECEPTOR IN CLEAR CELL RENAL CELL CARCINOMA AND INFILTRATING LYMPHOCYTES: IMPLICATIONS FOR CANCER INVASION, PROGNOSIS AND TUMOR IMMUNITY Masaru Ishida, Shuji Mikami, Takeo Kosaka, Ryuichi Mizuno, Eiji Kikuchi, Akira Miyajima, Ken Nakagawa, Yasunori Okada, and Mototsugu Oya Masaru IshidaMasaru Ishida More articles by this author , Shuji MikamiShuji Mikami More articles by this author , Takeo KosakaTakeo Kosaka More articles by this author , Ryuichi MizunoRyuichi Mizuno More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , Ken NakagawaKen Nakagawa More articles by this author , Yasunori OkadaYasunori Okada More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.744AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Aryl hydrocarbon receptor (AhR) is involved in xenobiotic-induced toxicity, and it is also associated with cancer cell invasion and tumor immunity. The aim of this study is to investigate the clinical significance of expression of AhR in RCC and infiltrating lymphocytes. Furthermore, we elucidate the role of AhR in cancer cells by regulating the expression using its ligand or siRNA for AhR in vitro. METHODS A total of 120 RCC patients were included in the study. The median age was 60 years (25 to 87) and the median follow-up was 63 months (0.3 to 151). The AhR expression in cancer cells and infiltrating lymphocytes in stromal tissues adjacent to cancer nests was investigated by immunohistochemistry and its associations with the clinicopathological parameters and prognosis were analyzed. AhR signal pathway was activated by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a ligand of AhR, or AhR expression was down-regulated by siRNA in an RCC cell line, 786-O. Subsequently, cancer cell invasion and expression of MMPs were investigated using MatrigelTM and real-time quantitative PCR. RESULTS The AhR expression in RCC and infiltrating lymphocytes was significantly higher in clear cell RCC compared to non-clear cell RCC (p < 0.05). Therefore, further experiments were confined to clear cell RCC. AhR in RCC was associated with the smoking history (p = 0.007), gender (p = 0.002) and histological grade (p = 0.02). The number of AhR-positive lymphocytes was significantly associated with AhR expression in RCC (p < 0.01), pathological T (p < 0.05), pathological N (p < 0.05), vascular invasion (p < 0.01) and metastasis (p < 0.05). A multivariate analysis revealed that the histological grade (p < 0.001), vascular invasion (p < 0.01) and AhR in cancer cells (p < 0.001) were independent prognostic factors for the PFS. The 5-year PFS rates were 80.5% in the low AhR RCC and 20.4% in the high AhR RCC (p < 0.001). TCDD treatment enhanced the cell invasion through MatrigelTM (p < 0.05) together with up-regulating the expression of MMP-1 and MMP-9 (p < 0.05). The cell invasion through MatrigelTM was inhibited in comparison to the cells transfected with a non-targeting siRNA (p < 0.05) together with the down-regulation of MMP-1 and MMP-9 (p < 0.05). CONCLUSIONS These results suggest that AhR in cancer cells regulates invasion of RCC and that AhR may be involved in tumor immunity. AhR could therefore be a potentially attractive therapeutic target for the control of RCC. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e304-e305 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Masaru Ishida More articles by this author Shuji Mikami More articles by this author Takeo Kosaka More articles by this author Ryuichi Mizuno More articles by this author Eiji Kikuchi More articles by this author Akira Miyajima More articles by this author Ken Nakagawa More articles by this author Yasunori Okada More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...