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.