Chondroitin sulfate content and decorin expression in glioblastoma are associated with proliferative activity of glioma cells and disease prognosis
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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.
KeywordsChondroitin sulfate proteoglycan Decorin Extracellular matrix Tumour microenvironment Glioblastoma multiforme
The authors would like to thank the ‘Proteomic analysis’ Center of the Institute of Molecular Biology and Biophysics (IMBB FRC FTM) for granting access to the equipment.
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).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in the study.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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