788 ABERRANT ACTIVATION OF PARACRINE LOOP BETWEEN PROSTATE CANCER CELLS AND CARCINOMA-ASSOCIATED FIBROBLASTS BY OVEREXPRESSION OF STROMAL INTERLEUKIN-6

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2012788 ABERRANT ACTIVATION OF PARACRINE LOOP BETWEEN PROSTATE CANCER CELLS AND CARCINOMA-ASSOCIATED FIBROBLASTS BY OVEREXPRESSION OF STROMAL INTERLEUKIN-6 Kenichiro Ishii, Yoichi Iwamoto, Manabu Kato, Kazuhiro Iguchi, Atsushi Mizokami, Kiminobu Arima, Taizo Shiraishi, and Yoshiki Sugimura Kenichiro IshiiKenichiro Ishii Tsu, Japan More articles by this author , Yoichi IwamotoYoichi Iwamoto Tsu, Japan More articles by this author , Manabu KatoManabu Kato Tsu, Japan More articles by this author , Kazuhiro IguchiKazuhiro Iguchi Gifu, Japan More articles by this author , Atsushi MizokamiAtsushi Mizokami Ishikawa, Japan More articles by this author , Kiminobu ArimaKiminobu Arima Tsu, Japan More articles by this author , Taizo ShiraishiTaizo Shiraishi Tsu, Japan More articles by this author , and Yoshiki SugimuraYoshiki Sugimura Tsu, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.876AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In the tumor microenvironment, activation of tumor-stromal interactions is considered to play a critical role in the promotion of tumorigenesis. During primary cancer progression, cancer cells generate the carcinoma-associated fibroblasts (CAFs) in adjacent normal fibroblasts, and then CAFs support the proliferation and invasion of adjacent cancer cells in a paracrine fashion. The serum level of interleukin-6 (IL-6) is a significant prognostic factor for prostate cancer (PCa) patients with disseminated diseases, suggesting positive roles of IL-6 in the aberrant activation of paracrine loop between PCa cells and CAFs. In this study, we investigated the relationship between responsiveness of PCa cells to stromal IL-6 and cellular AR signaling. METHODS The androgen-low-sensitive E9 cells were obtained from androgen-sensitive LNCaP cell population by limiting dilution method in regular culture condition. In contrast, the androgen-insensitive AIDL cells were established from LNCaP cells by continuous passaging in hormone-depleted condition. PCaSC-8 and PCaSC-9 cells were primary cultured from different human PCa specimens. RESULTS IL-6 and VEGF protein levels in both PCaSC-8 and PCaSC-9 cells were generally higher than normal human prostate stromal cells PrSC. In contrast to stromal cells, no IL-6 secretion from LNCaP, E9, and AIDL was detected. IL-6 treatment (10 ng/mL) suppressed cell proliferation of LNCaP and E9 accompanied with changes of cell morphology, i.e. induction of neuroendocrine-like differentiation. Induction of PSA secretion was observed only in IL-6-treated LNCaP. VEGF secretion was significantly increased in both IL-6-treated LNCaP and AIDL. A selective alpha1-adrenoceptor antagonist naftopidil (10 μM) but not tamsulosin suppressed IL-6-induced VEGF secretion in AIDL. CONCLUSIONS In this study, we have shown the evidence that secretions of IL-6 and VEGF from primary cultured CAFs derived PCa patients are generally higher than normal fibroblasts. Our results suggest that overexpression of stromal IL-6 might increase VEGF secretion from adjacent PCa cells in a paracrine fashion. Using LNCaP sublines, E9 and AIDL, differing in androgen-sensitivity, we demonstrated here that IL-6-induced VEGF secretion from PCa cells might be through cellular AR signaling-independent pathway. Identifying mechanisms underlying the aberrant activation of paracrine loop between PCa cells and CAFs is an initial step toward designing CAF-targeted therapy for treatment of PCa. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e322-e323 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kenichiro Ishii Tsu, Japan More articles by this author Yoichi Iwamoto Tsu, Japan More articles by this author Manabu Kato Tsu, Japan More articles by this author Kazuhiro Iguchi Gifu, Japan More articles by this author Atsushi Mizokami Ishikawa, Japan More articles by this author Kiminobu Arima Tsu, Japan More articles by this author Taizo Shiraishi Tsu, Japan More articles by this author Yoshiki Sugimura Tsu, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...