title: Restoration of desmosomal junction protein expression and inhibition of H3K9-specific histone demethylase activity by cytostatic proline-rich polypeptide-1 leads to suppression of tumorigenic potential in human chondrosarcoma cells.
abstract: Disruption of cell-cell junctions and the concomitant loss of polarity, downregulation of tumor-suppressive adherens junctions and desmosomes represent hallmark phenotypes for several different cancer cells. Moreover, a variety of evidence supports the argument that these two common phenotypes of cancer cells directly contribute to tumorigenesis. In this study, we aimed to determine the status of intercellular junction proteins expression in JJ012 human malignant chondrosarcoma cells and investigate the effect of the antitumorigenic cytokine, proline-rich polypeptide-1 (PRP-1) on their expression. The cell junction pathway array data indicated downregulation of desmosomal proteins, such as desmoglein (1,428-fold), desmoplakin (620-fold) and plakoglobin (442-fold). The tight junction proteins claudin 11 and E-cadherin were also downregulated (399- and 52-fold, respectively). Among the upregulated proteins were the characteristic for tumors gap junction β-5 protein (connexin 31.1) and the pro-inflammatory pathway protein intercellular adhesion molecule (upregulated 129- and 43-fold, respectively). We demonstrated that PRP-1 restored the expression of the abovementioned downregulated in chondrosarcoma desmosomal proteins. PRP-1 inhibited H3K9-specific histone demethylase activity in chondrosarcoma cells in a dose-dependent manner (0.5 µg/ml PRP, 63%; 1 µg/ml PRP, 74%; and 10 µg/ml PRP, 91% inhibition). Members of the H3K9 family were shown to transcriptionally repress tumor suppressor genes and contribute to cancer progression. Our experimental data indicated that PRP-1 restores tumor suppressor desmosomal protein expression in JJ012 human chondrosarcoma cells and inhibits H3K9 demethylase activity, contributing to the suppression of tumorigenic potential in chondrosarcoma cells.
authors.affiliation: Department of Orthopaedic Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Karina
authors.initials: K
authors.lastname: Galoian
authors.affiliation: Department of Orthopaedic Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Qureshi
authors.affiliation: Department of Orthopaedic Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Wideroff
authors.affiliation: University of Miami Tissue Bank Division, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: H T
authors.initials: HT
authors.lastname: Temple
keywords: H3K9-specific histone demethylase; cell-cell adhesion; chondrosarcoma; desmosomal proteins; proline-rich polypeptide-1