PD25-10 A NEWLY DISCOVERED COLLECTIVE MIGRATION OF UROTHELIAL CELLS: A POTENTIAL DEFENSE MECHANISM AGAINST BLADDER CANCER DEVELOPMENT

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD25-10 A NEWLY DISCOVERED COLLECTIVE MIGRATION OF UROTHELIAL CELLS: A POTENTIAL DEFENSE MECHANISM AGAINST BLADDER CANCER DEVELOPMENT Zhang Ning, Takeshi Sano, Ryosuke Ikeuchi, Hideaki Takada, Kenji Nakamura, Toru Sakatani, Akihiro Hamada, Yuki Kita, Michiyuki Matsuda, and Takashi Kobayashi Zhang NingZhang Ning More articles by this author , Takeshi SanoTakeshi Sano More articles by this author , Ryosuke IkeuchiRyosuke Ikeuchi More articles by this author , Hideaki TakadaHideaki Takada More articles by this author , Kenji NakamuraKenji Nakamura More articles by this author , Toru SakataniToru Sakatani More articles by this author , Akihiro HamadaAkihiro Hamada More articles by this author , Yuki KitaYuki Kita More articles by this author , Michiyuki MatsudaMichiyuki Matsuda More articles by this author , and Takashi KobayashiTakashi Kobayashi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003303.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Imaging of live animals at microscopic resolution (intravital imaging) found that bladder tumor (BT) development caused a unique collective migration of urothelial cells in a mouse orthotopic bladder cancer model. This study aimed to investigate the relationship between this newly discovered migration and BT growth. METHODS: MB49 cells (a mouse bladder cancer cell line) were labeled with a red fluorescent protein to distinguish them from urothelial cells of C57BL/6 mice expressing a cyan fluorescent protein. Labeled MB49 cells were then injected into mouse bladders pretreated with poly-l-lysine (PLL) to initiate BTs. While mice underwent general anesthesia using isoflurane, two-photon excitation microscopy, which enables deep tissue imaging, was performed to visualize the urothelium and the attached MB49 cells. Dasatinib, a Src/focal adhesion kinase signaling inhibitor, was intravenously or orally administered. RESULTS: A collective migration of urothelial cells was observed four days after intravesical injection of 1×106 MB49 cells (Figure 1). Pretreatment with PLL alone did not cause this migration. Intravenous and oral administration of dasatinib each remarkably retarded MB49-induced migration (Figure 2a). Surprisingly, inhibition of this migration by daily oral administration of dasatinib starting 24 hours after MB49 injection significantly enhanced BT growth despite dasatinib generally inhibiting cell-growth (Figure 2b). In a subcutaneous xenograft mouse model using MB49 cells, dasatinib slightly suppressed tumor growth. Intriguingly, transfer of urine from which cells had been removed by filtration from an MB49-injected bladder to another C57BL/6 mouse bladder caused the urothelial cell migration (Figure 2c). CONCLUSIONS: Cancer cell injection into the bladder caused a unique collective migration of urothelial cells. Inhibition of this migration enhances BT growth, suggesting that this migration may play a defensive role against BT development. We are currently working to identify the molecule(s) that trigger the migration. Enhancement of this migration may be a novel strategy for preventing BT recurrence after transurethral resection of BTs. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e733 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zhang Ning More articles by this author Takeshi Sano More articles by this author Ryosuke Ikeuchi More articles by this author Hideaki Takada More articles by this author Kenji Nakamura More articles by this author Toru Sakatani More articles by this author Akihiro Hamada More articles by this author Yuki Kita More articles by this author Michiyuki Matsuda More articles by this author Takashi Kobayashi More articles by this author Expand All Advertisement PDF downloadLoading ...