MP62-17 A NEW INSIGHT OF CELL-CELL INTERACTIONS IN TUMOR STROMA OF PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2016MP62-17 A NEW INSIGHT OF CELL-CELL INTERACTIONS IN TUMOR STROMA OF PROSTATE CANCER Kenichiro Ishii, Takeshi Sasaki, Manabu Miki, Manabu Kato, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, and Yoshiki Sugimura Kenichiro IshiiKenichiro Ishii More articles by this author , Takeshi SasakiTakeshi Sasaki More articles by this author , Manabu MikiManabu Miki More articles by this author , Manabu KatoManabu Kato More articles by this author , Hideki KandaHideki Kanda More articles by this author , Kiminobu ArimaKiminobu Arima More articles by this author , Taizo ShiraishiTaizo Shiraishi More articles by this author , and Yoshiki SugimuraYoshiki Sugimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.925AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Activation of tumor-stroma interactions plays 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. In the tumor microenvironment, CAFs communicate not only with cancer cells but also surrounding stromal cells. The tumor stroma consists not only of CAFs but also normal fibroblasts, myofibroblasts, or smooth muscle cells. Unfortunately, we know very little about cell-cell interactions in the tumor stroma. To investigate stromal cell-cell interactions, we performed in vitro co-culture experiments using primary cultured human prostate cancer (PCa) CAFs PCaSC-8 cells, and commercialized normal human prostate stromal cells PrSC and PrSMC. METHODS PCaSC-8 cells were isolated from needle biopsy samples of a PCa patient. PrSC and PrSMC were purchased from Lonza Group Ltd. Co-culture experiments were performed using cell culture inserts. RESULTS Cell growth of PrSC and PrSMC was significantly increased by co-culturing with PCaSC-8 cells, while that of PCaSC-8 cells was not affected by co-culturing neither with PrSC or PrSMC. In the condition of co-cultures with PCaSC-8 cells, mRNA expression of TNC, ACTA2 and FGF2 was significantly increased in PrSC. In contrast, expression of EGF, FGF7, HGF, and IGF1 mRNA was significantly increased in PrSMC. In PCaSC-8 cells, mRNA expression of ACTA2, HGF, and IGF1 was significantly increased by co-culturing with PrSC. In both PrSC and PrSMC, protein production of IL-6 was significantly increased by co-culturing with PCaSC-8 cells. In addition, VEGF in PrSC was significantly increased by co-culturing with PCaSC-8 cells. In PCaSC-8 cells, IL-6 and VEGF were significantly increased by co-culturing with PrSC. CONCLUSIONS We previously reported that PCa cells induced CAF-like differentiation in normal fibroblasts, i.e. PCa cells generate the CAFs. Here our results have demonstrated that normal fibroblasts co-cultured with CAFs become activated and exhibit the biochemical characteristics consistent with CAFs, i.e. CAFs also induce CAF-like differentiation in normal fibroblasts. Of interest, normal fibroblasts boost the biochemical characteristics of CAFs. Those cell-cell interactions in the tumor stroma suggest that CAFs may spread autonomously. In this cell competition, CAFs must be winner in the tumor stroma. Identifying mechanisms underlying the cell competition in the tumor stroma is an initial step toward designing CAF-targeted therapy for treatment of PCa. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e819 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Kenichiro Ishii More articles by this author Takeshi Sasaki More articles by this author Manabu Miki More articles by this author Manabu Kato More articles by this author Hideki Kanda More articles by this author Kiminobu Arima More articles by this author Taizo Shiraishi More articles by this author Yoshiki Sugimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...