Expression analysis and functional significance of chondroitin sulphate proteoglycans and heparan sulphate proteoglycans in prostrate cancer

Abstract

Glycosaminoglycans and proteoglycans have been found to be important regulators of cellular growth and metastasis. In this study, the expression of chondroitin sulphate (CS) and heparan sulphate (HS) in prostate cancer (CaP) tissues were analysed and their use as potential biomarkers were explored. To search for plausible novel therapeutic targets, the functional implications of CS and HS synthesis enzymes that were differently expressed in CaP were identified. Genome-wide expression profiling of CaP tissues compared to benign hyperplastic tissues were performed. It was found that CSGalNAcT-1was differentially expressed in prostate cancer. Immunohistochemistry was also performed and it was found that CS was upregulated in CaP and high CS expression augurs poor prognosis. Silencing CSGalNAcT-1, which initiates CS biosynthesis, inhibited cell growth and invasion, and promoted apoptosis via suppression of MAPRE-1, TPX2 and HIPK3. On the other hand, heparan sulphate detected using monoclonal 10E4 was not found to be differently expressed in prostate cancer. On the whole, my findings highlighted the importance of CS in cellular growth and behaviour, and suggested that CS may be a promising biomarker of CaP progression. The data also established the role of CSGalNAcT-1 as a pro-tumour protein.