MP21-06 CORTACTIN-MEDIATED INVADOPODIA FORMATION IS ESSENTIAL FOR TRANSUROTHELIAL INVASION AND EXTRAVASATION DURING BLADDER CANCER METASTASIS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2014MP21-06 CORTACTIN-MEDIATED INVADOPODIA FORMATION IS ESSENTIAL FOR TRANSUROTHELIAL INVASION AND EXTRAVASATION DURING BLADDER CANCER METASTASIS Kengo Imanishi, Noriko Tokui, Shingo Hatakeyama, Shigeru Tsuboi, Mihoko S. Yoneyama, Kanemitsu Yamaya, Tomihisa Funyu, and Chikara Ohyama Kengo ImanishiKengo Imanishi More articles by this author , Noriko TokuiNoriko Tokui More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Shigeru TsuboiShigeru Tsuboi More articles by this author , Mihoko S. YoneyamaMihoko S. Yoneyama More articles by this author , Kanemitsu YamayaKanemitsu Yamaya More articles by this author , Tomihisa FunyuTomihisa Funyu More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.834AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Invasive cancer cells form invadopodia, the filamentous actin (F-actin)-based membrane protrusions required for matrix degradation and invasion. Invadopodia are proposed to play a critical role in cancer cell invasion and metastasis because of their ability to degrade extracellular matrix. Cortactin is known to regulate the invadopodia formation in the process of bladder cancer metastasis. However, roles of cortactin-mediated invadopodia formation have not been fully characterized. Here, we investigated whether cortactin-mediated invadopodia formation is essential in invasion of bladder cancer cells through the urothelial and endothelial cell monolayer, and lung metastasis. METHODS The primary culture cells (P1, 2, 3, 4) were obtained from bladder cancer patients. The cell lines of RT4 (non-muscle invasive cancer cell line) and YTS-1 (muscle invasive cell lines) were used for in vitro and in vivo assay. Invadopodia formation and MMP-2 secretion were examined by immunofluorescence microscopy and gelatin zymography, respectively. Invasion capacity was evaluated by transurothelial and transendothelial invasion assays using primary human urothelial cells (HUC) and human microvascular endothelial cells from lung (HMVEC-L). To determine the role of cortactin in invadopodia formation and invasion, invasion assay and in vivo tumor formation assay were performed using cortactin knockdown YTS-1 (YTS-cortKD) cells with reduced invadopodia formation by silencing the expression of cortactin. RESULTS Cells from patients with muscle invasive bladder cancer exhibited a higher capacity to invade through the urothelial cell monolayer than cells from non-invasive bladder cancer. In addition, muscle invasive bladder cancer cells showed higher abilities to form invadopodia, and secrete MMP-2 than non-invasive cells. Cortactin knockdown YTS-1 cells with reduced invadopodia formation showed a markedly decreased capacity to invade through the urothelial and endothelial cell monolayer, and formation of metastatic foci in lung. CONCLUSIONS Our results suggest that cortactin-mediated invadopodia formation is a critical process for both transurothelial invasion, initial step of muscle invasion and cancer cell extravasation. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e227 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Kengo Imanishi More articles by this author Noriko Tokui More articles by this author Shingo Hatakeyama More articles by this author Shigeru Tsuboi More articles by this author Mihoko S. Yoneyama More articles by this author Kanemitsu Yamaya More articles by this author Tomihisa Funyu More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...