The Role of Adhesion Molecules as Biomarkers for the Aggressive Prostate Cancer Phenotype

Background: Currently available methods for diagnosis and staging of prostate cancer lack the sensitivity to distinguish between patients with indolent prostate cancer and those requiring radical treatment. Alterations in key adherens (AJ) and tight junction (TJ) components have been hailed as potential biomarkers for prostate cancer progression but the majority of research has been carried out on individual molecules. Objective: To elucidate a panel of biomarkers that may help distinguish dormant prostate cancer from aggressive metastatic disease. Methods: We analysed the expression of 7 well known AJ and TJ components in cell lines derived from normal prostate epithelial tissue (PNT2), non-invasive (CAHPV-10) and invasive prostate cancer (LNCaP, DU145, PC-3) using gene expression, western blotting and immunofluorescence techniques. Results: Claudin 7, alpha-catenin and beta-catenin protein expression were not significantly different between CAHPV-10 cells and PNT2 cells. However, in PC-3 cells, protein levels for claudin 7, alpha-catenin were significantly down regulated (21.5 fold, p=<.001) or undetectable respectively. Immunofluoresence showed beta-catenin localisation in PC-3 cells to be cytoplasmic as opposed to membraneous. Conclusion: These results suggest aberrant Claudin 7, alpha - and beta-catenin expression and/or localisation patterns may be putative markers for distinguishing localised prostate cancer from aggressive metastatic disease when used collectively.