MP21-10 DEVELOPMENT OF AN EFFICIENT BLADDER TUMOR MODEL BY RECOMBINING WITH MESENCHYMAL CELLS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2014MP21-10 DEVELOPMENT OF AN EFFICIENT BLADDER TUMOR MODEL BY RECOMBINING WITH MESENCHYMAL CELLS Kenichiro Ishii, Takeshi Sasaki, Manabu Kato, Kenjiro Ito, Motomu Sakuragi, Nobuyuki Oda, Hideki Kanda, Yasushi Yamada, Kiminobu Arima, Taizo Shiraishi, and Yoshiki Sugimura Kenichiro IshiiKenichiro Ishii More articles by this author , Takeshi SasakiTakeshi Sasaki More articles by this author , Manabu KatoManabu Kato More articles by this author , Kenjiro ItoKenjiro Ito More articles by this author , Motomu SakuragiMotomu Sakuragi More articles by this author , Nobuyuki OdaNobuyuki Oda More articles by this author , Hideki KandaHideki Kanda More articles by this author , Yasushi YamadaYasushi Yamada 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.2014.02.838AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Aberrant activation of tumor-stromal interactions is considered to play a critical role in the promotion of tumorigenesis. Many solid tumors are composed of carcinoma cells and surrounding stromal cells named as carcinoma-associated fibroblasts (CAFs). They secrete a number of growth factors such as EGF family, FGFs, HGF, and IGFs, which are also produced by rat mesenchymal cells (Ishii et al., Endocr Relate Cancer, 2009). Bladder cancer is the second most common genitourinary malignancy, with transitional cell carcinoma representing 90% of the cases. Unfortunately, bladder cancer has the high recurrence rate after treatment, even when superficial tumors are completely removed by a laser or electrical force. We hypothesize that the aberrant activation between stromal cells and bladder cancer cells is probably involved in the high recurrence rate of bladder cancer. The development of efficient tumor models that mimic human disease would benefit to investigate new cancer therapeutic agents. Here we have developed a new model of bladder tumors by recombining rat mesenchymal cells with T24 human bladder cancer cells. METHODS Rat mesenchymal cells were prepared from 18-day SD rat fetuses. Briefly, bladder, urogenital sinuses, and stomach were dissected from the fetuses and separated into epithelial and mesenchymal components. Recombinants were prepared by mixing 5 x 105 T24 cells and 1 x 105 rat mesenchymal cells in suspension. Pelleted cells were resuspended in neutralized type I rat tail collagen gels, and then grafted beneath the renal capsule of adult male nude mice. RESULTS As generally known, T24 tumors without rat mesenchymal cells were not well grown in vivo. In contrast, T24 tumors that formed with rat mesenchymal cells derived from urogenital sinus (UGM) and bladder (BLM) but not stomach (STM) showed accelerated cell proliferation and angiogenesis. In in vitro cell culture experiments, several growth factors such as EGF, TGF-alpha, and IL-6 stimulated cell proliferation of T24 cells. Only IL-6 treatment activated cellular PI3/Akt pathway in T24 cells, whereas IL-6 treatment reduced VEGF secretion from T24 cells. Cell motility of T24 cells was significantly increased by EGF and TGF-alpha treatment. CONCLUSIONS In this study, we demonstrate that our recombination model using mesenchymal cells may be useful to understand the tumor-stromal interactions in bladder cancer. Identifying mechanisms underlying the aberrant activation between stromal cells and bladder cancer cells is an initial step toward developing new cancer therapeutic agents in bladder cancer. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e229 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Kenichiro Ishii More articles by this author Takeshi Sasaki More articles by this author Manabu Kato More articles by this author Kenjiro Ito More articles by this author Motomu Sakuragi More articles by this author Nobuyuki Oda More articles by this author Hideki Kanda More articles by this author Yasushi Yamada 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 ...