title: Overexpression of caldesmon is associated with tumor progression in patients with primary non-muscle-invasive bladder cancer.
abstract: The expression and function of caldesmon (CAD) in urothelial bladder carcinoma (BC) have not been reported. Here, we investigated the expression, prognostic value, and potential functional mechanism of CAD in primary non-muscle-invasive bladder cancer (NMIBC). Protein profiling of tissue samples using antibody microarrays showed significantly higher CAD expression in muscle-invasive BC tissues compared with NMIBC tissues. We then validated the CAD expression in BC cells by immunohistochemistry analysis using paraffin-embedded tissue blocks and western blots using BC cell lines. In addition, we examined the expression of CAD variants by reverse transcription-polymerase chain reaction, and confirmed the expression of low-molecular-weight isoforms (L-CAD), specifically encoded by WI-38 L-CAD II (transcript variant 2), in BC cells. Survival analysis in an independent primary NMIBC cohort comprising 132 patients showed that positive CAD expression was significantly associated with poorer prognosis than no CAD expression with regard to recurrence- and progression-free survival (p = 0.001 and 0.014, respectively). Multivariate analyses further indicated that positive CAD expression was an independent predictor of progression-free survival (p = 0.032; HR = 5.983). Data obtained from in vitro silencing and overexpression studies indicated that L-CAD promotes migration and invasiveness of BC cells. Immunofluorescence assays showed dramatic structural changes in the actin cytoskeleton of BC cells after L-CAD overexpression. Our findings collectively suggest that L-CAD overexpression in primary NMIBC is significantly associated with tumor progression and that a possible mechanism for L-CAD's activity is implicated in increased cell motility and invasive characteristics through morphological changes in BC cells.
authors.affiliation: Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South Korea.
authors.forename: Myung-Shin
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South Korea.
authors.forename: Jisu
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pathology, Eulji University School of Medicine, Daejeon, South Korea.
authors.forename: Joo Heon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Hanjong
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Urology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, South Korea.
authors.forename: Jinsung
authors.initials: J
authors.lastname: Park
mesh_terms: D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D018613:Microscopy, Confocal; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D002148:Calmodulin-Binding Proteins; D020033:Protein Isoforms
keywords: antibody microarray; biomarkers; bladder cancer; caldesmon; tumor progression