Abstract

Background: HAVcR-1 has been linked to cancer aetiology and may regulate junctional complexes, with its role in prostate cancer still unexplored. This study aims to investigate the expression of HAVcR-1 in prostate cancer samples and the exploration of the cellular/molecular impact of HAVcR-1. Methods: Levels of HAVcR-1 ectodomain in the serum of prostate cancer patients were compared to healthy controls, and assessed as the total protein and gene expression of HAVcR-1 and tissues sections. The manipulation of HAVcR-1 levels within prostate cancer cell lines determined changes in cell behaviour using in vitro cell models and barrier function assays. Protein/phosphoprotein levels were assessed using Western blotting. Results: Levels of HAVcR-1 ectodomain from serum were decreased in patients with prostate cancer. Ectodomain levels correlated with the Gleason score. Histologically, the total protein/gene expression of HAVcR-1 was overexpressed in prostate cancer. The overexpression of HAVcR-1 in prostate cancer cell lines resulted in key changes in cell behaviour and the phosphorylation of β-catenin with a concurrent decrease in membranous E-cadherin, increased nuclear β-catenin and increased cyclin D1 protein expression, which were associated with HGF-promoted changes in the barrier function. Conclusions: HAVcR-1 expression and ectodomain release coincides with the presence of prostate cancer; thus, indicating HAVcR-1 as a potential biomarker to aid in diagnostics, and implicating HAVcR-1 in the dysregulation of junctional complexes.

Highlights

  • Publisher’s Note: MDPI stays neutralProstate cancer is the second most common cancer in males worldwide and the most common cancer in males in the UK, with approximately 1,111,000 and 43,436 new cases per year, respectively [1,2]

  • Serum HAVcR-1 ectodomain levels in prostate cancer: To investigate the release of the HAVcR-1 ectodomain into the circulation during the occurrence of prostate cancer, HAVcR-1 ectodomain levels were assessed in serum samples from patients with prostate cancer and from healthy controls using Enzyme-Linked Immunosorbent Assay (ELISA)

  • HAVcR-1 ectodomain levels were decreased in serum samples from the prostate cancer patient group (96.25 ± 32.85 pg/mL) compared to the serum samples from the healthy control group (208.46 ± 58.50 pg/mL), (p < 0.0001), Figure 1A

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Summary

Introduction

Publisher’s Note: MDPI stays neutralProstate cancer is the second most common cancer in males worldwide and the most common cancer in males in the UK, with approximately 1,111,000 and 43,436 new cases per year, respectively [1,2]. Diagnostic techniques, are still reliant on the inherently flawed PSA blood test, which has limited associated risks in comparison to other invasive testing, such as prostate biopsies, which may result in a subsequent infection and urinary incontinence [3,4]. It is, important to identify novel biomarkers that can be used to improve the accuracy of low invasive testing. The overexpression of HAVcR-1 in prostate cancer cell lines resulted in key changes in cell behaviour and the phosphorylation of β-catenin with a concurrent decrease in membranous E-cadherin, increased nuclear β-catenin and increased cyclin D1 protein expression, which were associated with HGF-promoted changes in the barrier function. Conclusions: HAVcR-1 expression and ectodomain release coincides with the presence of prostate cancer; indicating HAVcR-1 as a potential biomarker to aid in diagnostics, and implicating HAVcR-1 in the dysregulation of junctional complexes

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