Oncotarget

Clinical Research Papers:

Overexpression of caldesmon is associated with tumor progression in patients with primary non-muscle-invasive bladder cancer

Myung-Shin Lee, Jisu Lee, Joo Heon Kim, Won Tae Kim, Wun-Jae Kim, Hanjong Ahn and Jinsung Park _

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Oncotarget. 2015; 6:40370-40384. https://doi.org/10.18632/oncotarget.5458

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Abstract

Myung-Shin Lee1, Jisu Lee1, Joo Heon Kim2, Won Tae Kim3, Wun-Jae Kim3, Hanjong Ahn4, Jinsung Park5

1Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South Korea

2Department of Pathology, Eulji University School of Medicine, Daejeon, South Korea

3Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea

4Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

5Department of Urology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, South Korea

Correspondence to:

Jinsung Park, e-mail: jspark.uro@gmail.com

Keywords: antibody microarray, bladder cancer, biomarkers, caldesmon, tumor progression

Received: June 21, 2015     Accepted: September 15, 2015     Published: September 25, 2015

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.


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