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

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 malignan...

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Autores principales: Ushakov, Victor S., Tsidulko, Alexandra Y., de La Bourdonnaye, Gabin, Kazanskaya, Galina M., Volkov, Alexander M., Kiselev, Roman S., Kobozev, Vyacheslav V., Kostromskaya, Diana V., Gaytan, Alexey S., Krivoshapkin, Alexei L., Aidagulova, Svetlana V., Grigorieva, Elvira V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713271/
https://www.ncbi.nlm.nih.gov/pubmed/29104277
http://dx.doi.org/10.3390/ijms18112301
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author Ushakov, Victor S.
Tsidulko, Alexandra Y.
de La Bourdonnaye, Gabin
Kazanskaya, Galina M.
Volkov, Alexander M.
Kiselev, Roman S.
Kobozev, Vyacheslav V.
Kostromskaya, Diana V.
Gaytan, Alexey S.
Krivoshapkin, Alexei L.
Aidagulova, Svetlana V.
Grigorieva, Elvira V.
author_facet Ushakov, Victor S.
Tsidulko, Alexandra Y.
de La Bourdonnaye, Gabin
Kazanskaya, Galina M.
Volkov, Alexander M.
Kiselev, Roman S.
Kobozev, Vyacheslav V.
Kostromskaya, Diana V.
Gaytan, Alexey S.
Krivoshapkin, Alexei L.
Aidagulova, Svetlana V.
Grigorieva, Elvira V.
author_sort Ushakov, Victor S.
collection PubMed
description 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 heterogeneity of the presence of the HPSE protein. The detected disorganisation of the HS biosynthetic system in gliomas might be a potential molecular mechanism for the changes of HS structure and content in tumour microenvironments, contributing to the invasion of glioma cells and the development of the disease.
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spelling pubmed-57132712017-12-07 Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation Ushakov, Victor S. Tsidulko, Alexandra Y. de La Bourdonnaye, Gabin Kazanskaya, Galina M. Volkov, Alexander M. Kiselev, Roman S. Kobozev, Vyacheslav V. Kostromskaya, Diana V. Gaytan, Alexey S. Krivoshapkin, Alexei L. Aidagulova, Svetlana V. Grigorieva, Elvira V. Int J Mol Sci Article 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 heterogeneity of the presence of the HPSE protein. The detected disorganisation of the HS biosynthetic system in gliomas might be a potential molecular mechanism for the changes of HS structure and content in tumour microenvironments, contributing to the invasion of glioma cells and the development of the disease. MDPI 2017-11-01 /pmc/articles/PMC5713271/ /pubmed/29104277 http://dx.doi.org/10.3390/ijms18112301 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ushakov, Victor S.
Tsidulko, Alexandra Y.
de La Bourdonnaye, Gabin
Kazanskaya, Galina M.
Volkov, Alexander M.
Kiselev, Roman S.
Kobozev, Vyacheslav V.
Kostromskaya, Diana V.
Gaytan, Alexey S.
Krivoshapkin, Alexei L.
Aidagulova, Svetlana V.
Grigorieva, Elvira V.
Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation
title Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation
title_full Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation
title_fullStr Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation
title_full_unstemmed Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation
title_short Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation
title_sort heparan sulfate biosynthetic system is inhibited in human glioma due to ext1/2 and hs6st1/2 down-regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713271/
https://www.ncbi.nlm.nih.gov/pubmed/29104277
http://dx.doi.org/10.3390/ijms18112301
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