Research output: Contribution to journal › Article › peer-review
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 et al.
In: International Journal of Molecular Sciences, Vol. 18, No. 11, 2301, 01.11.2017.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Heparan sulfate biosynthetic system is inhibited in human glioma due to EXT1/2 and HS6ST1/2 down-regulation
AU - Ushakov, Victor S.
AU - Tsidulko, Alexandra Y.
AU - De La Bourdonnaye, Gabin
AU - Kazanskaya, Galina M.
AU - Volkov, Alexander M.
AU - Kiselev, Roman S.
AU - Kobozev, Vyacheslav V.
AU - Kostromskaya, Diana V.
AU - Gaytan, Alexey S.
AU - Krivoshapkin, Alexei L.
AU - Aidagulova, Svetlana V.
AU - Grigorieva, Elvira V.
N1 - Publisher Copyright: © 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - Biosynthesis
KW - Extracellular matrix
KW - Glioma
KW - Heparan sulfate
KW - Heparanase
KW - Invasion
KW - Sulfotransferase
KW - Tumour microenvironment
KW - PROTEOGLYCANS
KW - heparanase
KW - sulfotransferase
KW - CANCER
KW - heparan sulfate
KW - invasion
KW - ROLES
KW - biosynthesis
KW - GROWTH
KW - glioma
KW - tumour microenvironment
KW - EXTRACELLULAR-MATRIX
KW - EXPRESSION
KW - extracellular matrix
UR - http://www.scopus.com/inward/record.url?scp=85033573744&partnerID=8YFLogxK
U2 - 10.3390/ijms18112301
DO - 10.3390/ijms18112301
M3 - Article
C2 - 29104277
AN - SCOPUS:85033573744
VL - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 11
M1 - 2301
ER -
ID: 9698556