Proteoglycans (PGs) are expressed on the cell surface and extracellular matrix of all mammalian cells and tissues, playing an important role in cell-cell and cell-matrix interactions and signaling. Changes in the expression and functional properties of individual PGs in prostate cancer are shown, although common patterns of PGs expression in normal and tumour prostate tissues remain unknown. In this study, expression of cell surface and stromal proteoglycans (glypican-1, perlecan, syndecan-1, aggrecan, versican, NG2, brevican, decorin, and lumican) in normal tissue and prostate tumours was determined by RT-PCR analysis and immunostaining with core protein- and GAG-specific antibodies. In normal human prostate tissue, versican, decorin, and biglycan were predominant proteoglycans localised in tissue stroma, and syndecan-1 and glypican-1 were expressed mainly by epithelial cells. In prostate tumours, complex changes in proteoglycans occur, with a common trend towards decrease of decorin and lumican expression, overall increase of syndecan-1 and glypican-1 expression in tumour stroma along with its disappearance in tumour epithelial cells, and aggrecan and NG2 expressions in some prostate tumours. All the changes result in the highly individual proteoglycan expression patterns in different prostate tumours, which may be potentially useful as molecular markers for prostate cancer personalised diagnosis and treatment.

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BackgroundD-glucuronyl C5-epimerase (GLCE) is one of the key enzymes in the biosynthesis of heparansulfate proteoglycans. Down-regulation of GLCE expression in human breast tumours suggests a possible involvement of the gene in carcinogenesis. In this study, an effect of GLCE ectopic expression on cell proliferation and viability of breast carcinoma cells MCF7 in vitro and its potential molecular mechanisms were investigated.ResultsD-glucuronyl C5-epimerase expression was significantly decreased in MCF7 cells compared to normal human breast tissue. Re-expression of GLCE inhibited proliferative activity of MCF7 cells according to CyQUANT NF Cell Proliferation Assay, while it did not affect their viability in Colony Formation Test. According to Cancer PathFinder RT Profiler PCR Array, antiproliferative effect of GLCE in vitro could be related to the enhanced expression of tumour suppressor genes р53 (+3.3 fold), E2F1 (+3.00 fold), BRCA1 (+3.5 fold), SYK (+8.1 fold) and apoptosis-related genes BCL2 (+4.2 fold) and NFKB1 (+2.6 fold). Also, GLCE re-expression in MCF7 cells considerably changed the expression of some genes involved in angiogenesis (IL8, +4.6 fold; IFNB1, +3.9 fold; TNF, +4.6 fold and TGFB1, -5.7 fold) and invasion/metastasis (SYK, +8.1 fold; NME1, +3.96 fold; S100A4, -4.6 fold).ConclusionsThe ability of D-glucuronyl С5-epimerase to suppress proliferation of breast cancer cells MCF7 through the attenuated expression of different key genes involved in cell cycle regulation, angiogenesis and metastasis molecular pathways supports the idea on the involvement of the gene in regulation of breast cancer cell proliferation.