Oncotarget

Research Papers:

Wnt5a / planar cell polarity signaling pathway in urothelial carcinoma, a potential prognostic biomarker

Mark Saling, Jordan K. Duckett, Ian Ackers, Karen Coschigano, Scott Jenkinson and Ramiro Malgor _

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Oncotarget. 2017; 8:31655-31665. https://doi.org/10.18632/oncotarget.15877

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Abstract

Mark Saling1, Jordan K. Duckett1, Ian Ackers1, Karen Coschigano1,2,3, Scott Jenkinson4 and Ramiro Malgor1,2,3

1Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA

2Interdisciplinary Program in Molecular and Cellular Biology, Ohio University, Athens, Ohio, USA

3The Diabetes Institute of Ohio University, Athens, Ohio, USA

4University Medical Associates, Inc., Pathology, Athens, Ohio, USA

Correspondence to:

Ramiro Malgor, email: malgor@ohio.edu

Keywords: urothelial carcinoma, bladder, Wnt5a, epithelial mesenchymal transition, biomarker

Received: August 25, 2016    Accepted: February 01, 2017    Published: March 03, 2017

ABSTRACT

Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. Bladder cancers detected at an early stage have a very high five-year survival rate, but when detected after local metastasis the rate is only about 50%. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of this study was to analyze UC cases reported in Athens, Ohio and investigate the major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines.

Formalin fixed and paraffin embedded transurethral resection tissues were immunostained for Wnt5a, Ror-2, CTHRC1 and E-cadherin. In addition, in vitro studies using UC cell lines were investigated for Wnt5a/PCP signaling and epithelial mesenchymal transition (EMT) gene expression. The IHC results showed a correlation between the expression of Wnt5a, Ror2 and CTHRC1 with high histological grade of the tumor, while E-cadherin showed an opposite trend of expression. Real time RT-PCR results showed that RNA expression of the Wnt5a/ PCP pathway genes vary in low and high grade UC cell lines and that the high grade cell lines exhibited signs of EMT.

These findings support that Wnt5a-Ror2 signaling plays a role in UC, support the potential use of Wnt5a as a prognostic marker and provide evidence that Wnt5a signaling may be used as an effective molecular target for novel therapeutic tools.


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