MP03-14 INHIBITION OF HUMAN DETRUSOR SMOOTH MUSCLE CELL GROWTH AND MODULATION OF CYTOSKELETAL ORGANIZATION BY IMMUNO-MODULATORY IMIDE DRUGS (IMIDS)

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP03-14 INHIBITION OF HUMAN DETRUSOR SMOOTH MUSCLE CELL GROWTH AND MODULATION OF CYTOSKELETAL ORGANIZATION BY IMMUNO-MODULATORY IMIDE DRUGS (IMIDS) Alexander Tamalunas, Amin Wendt, Florian Springer, Ru Huang, Ruixiao Wang, Yuhan Liu, Beata Rutz, Anna Ciotkowska, Giuseppe Magistro, Christian Stief, and Martin Hennenberg Alexander TamalunasAlexander Tamalunas More articles by this author , Amin WendtAmin Wendt More articles by this author , Florian SpringerFlorian Springer More articles by this author , Ru HuangRu Huang More articles by this author , Ruixiao WangRuixiao Wang More articles by this author , Yuhan LiuYuhan Liu More articles by this author , Beata RutzBeata Rutz More articles by this author , Anna CiotkowskaAnna Ciotkowska More articles by this author , Giuseppe MagistroGiuseppe Magistro More articles by this author , Christian StiefChristian Stief More articles by this author , and Martin HennenbergMartin Hennenberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While lower urinary tract symptoms (LUTS) consist of voiding (BPH) and storage disorders (OAB), new AUA and EAU guidelines take into account the mounting number of patients suffering from both, so called “mixed LUTS”. Recently, we could show that IMiDs (thalidomide, lenalidomide and pomalidomide) inhibit prostate smooth muscle contraction, modulate cytoskeletal actin organization, and reduce prostate stromal cell growth at the same time, without showing cytotoxic effects. Based on these promising data, we now investigated the effects of IMiDs on cellular functions, including cytoskeletal organization, and growth in bladder cells. METHODS: Experiments were carried out in an immortalized line of cultured human bladder detrusor smooth muscle cells (HBdSMC). Cytoskeletal organization was visualized by phalloidin staining, while cell growth was assessed using an EdU and cell colony assay. Cell viability was quantified in CCK8 assay, and FACS. RESULTS: IMiDs ([A] thalidomide 10-100 µM, [B] lenalidomide 5-30 µM, and [C] pomalidomide 2.5-10 µM) significantly reduced the number of viable WPMY-1 cells in a concentration- and time-dependent manner (Figure 1). Correspondingly, proliferation of WPMY-1 cells was significantly reduced in a concentration-dependent manner (Figure 2 and 3), without showing pro-apoptotic effects (Figure 4). In parallel, IMiDs induced cytoskeletal disorganization: while the cellular shape of control cells was characterized by many long and thin protrusions containing bundles of actin filaments, this structure collapsed after treatment with IMiDs (Figure 5). CONCLUSIONS: IMiDs impair human detrusor smooth muscle growth, which is paralleled by a breakdown of the cytoskeleton, which may inhibit exaggerated bladder smooth muscle contraction in OAB. Urodynamic effects in vivo and a possible application in LUTS appear possible. Together with our previous data, this may suggest a possible novel drug class in LUTS treatment. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e27 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Tamalunas More articles by this author Amin Wendt More articles by this author Florian Springer More articles by this author Ru Huang More articles by this author Ruixiao Wang More articles by this author Yuhan Liu More articles by this author Beata Rutz More articles by this author Anna Ciotkowska More articles by this author Giuseppe Magistro More articles by this author Christian Stief More articles by this author Martin Hennenberg More articles by this author Expand All Advertisement PDF downloadLoading ...