MP45-08 STABILIZATION OF INVADOPODIA BY PLECTIN- MEDIATED CONJUNCTION TO VIMENTIN INTERMEDIATE FILAMENT IS A CRITICAL MOLECULAR STEP OF INVASION AND EXTRAVASATION FOR METASTASIS IN BLADDER CANCER.

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2016MP45-08 STABILIZATION OF INVADOPODIA BY PLECTIN- MEDIATED CONJUNCTION TO VIMENTIN INTERMEDIATE FILAMENT IS A CRITICAL MOLECULAR STEP OF INVASION AND EXTRAVASATION FOR METASTASIS IN BLADDER CANCER. Mihoko Sutoh Yoneyama, Shingo Hatakeyama, Tomonori Habuchi, Takamitsu Inoue, Toshiya Nakamura, Tomihisa Funyu, Gerhard Wiche, Shigeru Tsuboi, and Chikara Ohyama Mihoko Sutoh YoneyamaMihoko Sutoh Yoneyama More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Tomonori HabuchiTomonori Habuchi More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Toshiya NakamuraToshiya Nakamura More articles by this author , Tomihisa FunyuTomihisa Funyu More articles by this author , Gerhard WicheGerhard Wiche More articles by this author , Shigeru TsuboiShigeru Tsuboi More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.285AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To investigate the molecular mechanisms of bladder cancer (BCa) metastasis, we previously isolated a high-metastatic BCa cell subpopulation from a low-metastatic cell line by using an in vivo selection system (Sugiyama et al Oncol. Res. 20, 289-295). The high-metastatic BCa cell subpopulation showed a high ability to form invadopodia, the filamentous (F-) actin-based membrane protrusions that play an essential role in cancer cell invasion. Analysis of gene expression profiles revealed that the expression of an intermediate filament (IF) protein, vimentin and a cytoskeletal linker protein, plectin was up-regulated in the high-metastatic BCa cells compared with the low-metastatic BCa cell line. Here we report a novel molecular mechanism of invasive bladder cancer cell extravasation using vimentin IF and plectin. METHODS Six human BCa cell lines (RT-4, 5637, KK-47, T24, BOY and YTS-1) and primary culture of BCa cells from three genetically independent patients were used. The expression of vimentin and plectin in BCa cells was assessed by immunoblotting. The interaction between vimentin and plectin was examined by immunoprecipitation. The spatial correlation between vimentin, plectin and F-actin in BCa cells was analyzed by confocal microscopy. To evaluate the functions of invadopodia, cells were assayed for extracellular matrix (ECM) degradation, Matrigel invasion, transendothelial invasion and lung metastasis. RESULTS In invasive BCa cells, the expression levels of vimentin and plectin were elevated and the vimentin IF-plectin-invadopodia F-actin link was formed. Disruption of this link severely impaired invadopodia formation, reducing the capacities of ECM degradation, Matrigel invasion, transendothelial invasion and metastasis. In addition, the vimentin assembly into the filaments was required for invadepodia formation. CONCLUSIONS Our results strongly suggest that plectin anchoring invadopodia to vimentin IF scaffolds and stabilizes invadopodia, which is a critical molecular step for BCa cell invasion and extravasation for metastasis. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e610-e611 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Mihoko Sutoh Yoneyama More articles by this author Shingo Hatakeyama More articles by this author Tomonori Habuchi More articles by this author Takamitsu Inoue More articles by this author Toshiya Nakamura More articles by this author Tomihisa Funyu More articles by this author Gerhard Wiche More articles by this author Shigeru Tsuboi More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...