Identification of Extracellular δ-Catenin Accumulation for Prostate Cancer Detection

BACKGROUND. Prostate cancer is the second leading cause of cancer death in men, and early detection is essential to reduce mortality and increase survival. delta-Catenin is a unique beta-catenin superfamily protein primarily expressed in the brain but is upregulated in human prostatic adenocarcinomas. Despite its close correlation with the disease, it is unclear whether delta-catenin presents the potential in prostate cancer screening because it is an intracellular protein. In this study, we investigated the hypothesis of delta-catenin accumulation in the urine of prostate cancer patients and its potential pathways of excretion into extracellular milieu. METHODS. Prostate cancer cell cultures, human tissue biopsies, and voided urines were characterized to determine extracellular delta-catenin accumulation and co-isolation with exosomes/prostasomes. RESULTS. We identified delta-catenin in culture media and in the stroma of human prostate cancer tissues. In PC-3 cells in culture, delta-catenin was partially co-localized and co-isolated with raft-associated membrane protein caveolin-1 and glycosylphosphatidylinositol-anchored protein CD59, suggesting its potential excretion into extracellular milieu through exosome/prostasome associated pathways. Interference with endocytic pathway using wortmannin did not block prostasome excretion, but delta-catenin overexpression promoted the extracellular accumulation of caveolin-1. delta-Catenin, caveolin-1, and CD59 were all detected in cell-free human voided urine prostasomes. delta-Catenin immunoreactivity was significantly increased in the urine of prostate cancer patients (P < 0.0005). CONCLUSIONS. This study demonstrated, for the first time, the extracellular accumulation of delta-catenin in urine supporting its potential utility for non-invasive prostate cancer detection. Prostate 69: 411-418, 2009. (C) 2008 Wiley-Liss, Inc.