Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation

International Journal of Molecular Sciences
Victor S UshakovElvira V Grigorieva

Abstract

Heparan sulfate (HS) is an important component of the extracellular matrix and cell surface, which plays a key role in cell-cell and cell-matrix interactions. Functional activity of HS directly depends on its structure, which determined by a complex system of HS biosynthetic enzymes. During malignant transformation, the system can undergo significant changes, but for glioma, HS biosynthesis has not been studied in detail. In this study, we performed a comparative analysis of the HS biosynthetic system in human gliomas of different grades. RT-PCR analysis showed that the overall transcriptional activity of the main HS biosynthesis-involved genes (EXT1, EXT2, NDST1, NDST2, GLCE, HS2ST1, HS3ST1, HS3ST2, HS6ST1, HS6ST2, SULF1, SULF2, HPSE) was decreased by 1.5-2-fold in Grade II-III glioma (p < 0.01) and by 3-fold in Grade IV glioma (glioblastoma multiforme, GBM) (p < 0.05), as compared with the para-tumourous tissue. The inhibition was mainly due to the elongation (a decrease in EXT1/2 expression by 3-4-fold) and 6-O-sulfation steps (a decrease in 6OST1/2 expression by 2-5-fold) of the HS biosynthesis. Heparanase (HPSE) expression was identified in 50% of GBM tumours by immunostaining, and was characterised by a high intratumoural...Continue Reading

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Citations

Feb 23, 2020·International Journal of Molecular Sciences·Anastasia V SuhovskihElvira V Grigorieva
May 31, 2018·Cancer Biomarkers : Section a of Disease Markers·Yunxiao LyuSicong Zhao
Sep 13, 2020·International Journal of Molecular Sciences·Valeria De Pasquale, Luigi Michele Pavone
Dec 9, 2021·Advanced Healthcare Materials·Chaitanya Tondepu, Lohitash Karumbaiah

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