TY - JOUR

T1 - Chondroitin sulfate content and decorin expression in glioblastoma are associated with proliferative activity of glioma cells and disease prognosis

AU - Tsidulko, Alexandra Y.

AU - Kazanskaya, Galina M.

AU - Volkov, Alexander M.

AU - Suhovskih, Anastasia V.

AU - Kiselev, Roman S.

AU - Kobozev, Vyacheslav V.

AU - Gaytan, Alexei S.

AU - Krivoshapkin, Alexei L.

AU - Aidagulova, Svetlana V.

AU - Grigorieva, Elvira V.

N1 - Funding Information: This study was funded by the Russian Science Foundation, grant number 16-15-10243. AYT was supported by a scholarship of Russian Federation President for young scientists (SP-5435.2018.4). AVS was supported by a scholarship of Russian Federation President for young scientists (SP-1816.2019.4). Publisher Copyright: © 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Chondroitin sulfate proteoglycans (CSPGs) are important components of brain extracellular matrix (ECM), although their contribution in gliomagenesis remains underinvestigated. Here, both chondroitin sulfate (CS) content/distribution and expression of a number of CSPG core proteins were studied in glioblastoma multiforme (GBM) tumours with different prognosis (n = 40) using immunohistochemistry and RT-PCR analysis. Survival rates for clinically different patient groups were compared using the Kaplan-Meier analysis and univariate Cox model. CS content was increased in 60–65% of studied GBM tumours and distributed heterogeneously, mainly at perinecrotic and perivascular zones rather than tumour cells with specific morphology. CS accumulation, especially in the tumour extracellular matrix, was positively associated with the proliferative activity of GBM cells according to theKi67 index (p < 0.01) but revealed no significant association with age or sex of the patients, tumour localisation, relapse or disease outcome. The increase in CS content in GBM tumours was accompanied by upregulation of decorin (1.5-fold), biglycan (3-fold) and serglycin (2-fold) expression (p < 0.05), while only decorin expression level was negatively associated with the overall survival rate of the GBM patients (p < 0.05). These results demonstrate a contribution of CS to high intratumoural heterogeneity of GBM and suggest CS content and decorin expression for further investigation as potential microenvironmental glycomarkers/targets for GBM diagnostics and treatment.

AB - Chondroitin sulfate proteoglycans (CSPGs) are important components of brain extracellular matrix (ECM), although their contribution in gliomagenesis remains underinvestigated. Here, both chondroitin sulfate (CS) content/distribution and expression of a number of CSPG core proteins were studied in glioblastoma multiforme (GBM) tumours with different prognosis (n = 40) using immunohistochemistry and RT-PCR analysis. Survival rates for clinically different patient groups were compared using the Kaplan-Meier analysis and univariate Cox model. CS content was increased in 60–65% of studied GBM tumours and distributed heterogeneously, mainly at perinecrotic and perivascular zones rather than tumour cells with specific morphology. CS accumulation, especially in the tumour extracellular matrix, was positively associated with the proliferative activity of GBM cells according to theKi67 index (p < 0.01) but revealed no significant association with age or sex of the patients, tumour localisation, relapse or disease outcome. The increase in CS content in GBM tumours was accompanied by upregulation of decorin (1.5-fold), biglycan (3-fold) and serglycin (2-fold) expression (p < 0.05), while only decorin expression level was negatively associated with the overall survival rate of the GBM patients (p < 0.05). These results demonstrate a contribution of CS to high intratumoural heterogeneity of GBM and suggest CS content and decorin expression for further investigation as potential microenvironmental glycomarkers/targets for GBM diagnostics and treatment.

KW - Chondroitin sulfate proteoglycan

KW - Decorin

KW - Extracellular matrix

KW - Glioblastoma multiforme

KW - Tumour microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85075600807&partnerID=8YFLogxK

U2 - 10.1007/s00441-019-03127-2

DO - 10.1007/s00441-019-03127-2

M3 - Article

C2 - 31773303

AN - SCOPUS:85075600807

VL - 379

SP - 147

EP - 155

JO - Cell and Tissue Research

JF - Cell and Tissue Research

SN - 0302-766X

IS - 1

ER -