990 SPANXB2 EXPRESSION INCREASES PROSTATE CANCER AGGRESSIVITY: A NEW VIEW OF STROMAL-EPITHELIAL CELL INTERACTION

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research (V)1 Apr 2013990 SPANXB2 EXPRESSION INCREASES PROSTATE CANCER AGGRESSIVITY: A NEW VIEW OF STROMAL-EPITHELIAL CELL INTERACTION Hangwen Li, Ericka Diallo Kou, James Hernandez, Steven Ressler, Arun Sreekumar, Gustavo Ayala, David Rowley, Kenneth Pienta, and Ganesh Palapattu Hangwen LiHangwen Li Ann Arbor, MI More articles by this author , Ericka Diallo KouEricka Diallo Kou houston, TX More articles by this author , James HernandezJames Hernandez Ann Arbor, MI More articles by this author , Steven ResslerSteven Ressler houston, TX More articles by this author , Arun SreekumarArun Sreekumar houston, TX More articles by this author , Gustavo AyalaGustavo Ayala houston, TX More articles by this author , David RowleyDavid Rowley houston, TX More articles by this author , Kenneth PientaKenneth Pienta Ann Arbor, MI More articles by this author , and Ganesh PalapattuGanesh Palapattu Ann Arbor, MI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.572AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Critical problems in prostate cancer lie on our inability to reliably distinguish indolent from aggressive disease and effectively treat metastatic lesions. Recent evidence has implicated a class of genes, termed Cancer Testis Antigens (CTA), that are uniquely expressed in malignant tissue and are associated with cancer progression and metastasis. CTA SPANXB2 has been reported to be associated with aggressive stage of melanoma. Here, we sought to investigate the uncertain role of SPANXB2 on prostate cancer metastasis under the regulation of stromal-epithelial interaction. METHODS SPANXB2 was identified from a cross of the CTA bank and a metastatic gene signature derived from a highly metastatic prostate orthotopic xenograft model. An in vitro epithelial-stroma interaction model was established by co-culture of GFP labeled PC3, Du145 or LNCaP with HSP19I (a prostate stromal line derived from a 19 year old healthy donor). GFP+ cancer cells were sorted out via FACS. Some of these sorted cells were then further treated with HSP19I again and re-sorted by FACS. GFP+ cells were then used to perform functional assays assessing proliferation, invasion and migration. In vivo orthotropic xenograft experiments were also performed. Real time PCR was performed to detect SPANXB2 levels. ELISA kit was used to detect TGF-β2 levels from conditioned medium obtained from epithelial-stroma model co-cultures. RESULTS SPANXB2 levels were significantly increased 8-10 fold with HSP19I treatment, and increased with additional epithelial cell exposure to HSP19I. HSP-19I promoted the abilities of proliferation, migration, and invasion in prostate cancer lines . Moreover, co-injection of HSP-19I with PC3 cells strongly promoted metastasis in a mouse dorsal prostate injection model. Additionally, TGF-β2 levels were significantly increased in cancer cells exposure to HSP19I . Interestingly, TGF-β2 treatment of cancer cells also increased SPANXB2 levels in culture. CONCLUSIONS We observed that co-culture of human prostate cancer epithelial cells with human prostate stromal cells increases cancer cell biological aggressiveness and is associated with increased cancer cell expression of SPANXB2. Intriguingly, in this model, SPANXB2 expression is associated with TGF-β2 exposure. Further work is needed to clarify the role of SPANXB2 expression in mediating prostate cancer progression. Targeting stromal-epithelial cell interactions, such as stromal induced epithelial expression of SPANXB2, remains a potential novel therapeutic target. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e406 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hangwen Li Ann Arbor, MI More articles by this author Ericka Diallo Kou houston, TX More articles by this author James Hernandez Ann Arbor, MI More articles by this author Steven Ressler houston, TX More articles by this author Arun Sreekumar houston, TX More articles by this author Gustavo Ayala houston, TX More articles by this author David Rowley houston, TX More articles by this author Kenneth Pienta Ann Arbor, MI More articles by this author Ganesh Palapattu Ann Arbor, MI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...