Multiple Irradiation Affects Cellular and Extracellular Components of the Mouse Brain Tissue and Adhesion and Proliferation of Glioblastoma Cells in Experimental System In Vivo

International Journal of Molecular Sciences

Konstantin E. Kuper¹  Oxana A. Pashkovskaya²  Alexander M. Volkov²  Evgenii E. Kliver²  Alexander A. Zheravin²  Dmitry K. Sokolov³  Lyubov S. Klyushova³  Alexandra Y. Tsidulko³  Svetlana V. Aidagulova³  Anastasia V. Suhovskih³  Elvira V. Grigorieva³  Maxim O. Politko³  Galina M. Kazanskaya³ 

[1] Budker Institute of Nuclear Physics SB RAS, 630090 Novosibirsk, Russia;E.N. Meshalkin National Medical Research Center, 630055 Novosibirsk, Russia;Institute of Molecular Biology and Biophysics, FRC FTM, 630060 Novosibirsk, Russia;

关键词: glioblastoma;    radiotherapy;    tumor microenvironment;    extracellular matrix;    glycosylation;    mouse brain irradiation;   

DOI  :  10.3390/ijms222413350

来源: DOAJ

【 摘 要 】

Intensive adjuvant radiotherapy (RT) is a standard treatment for glioblastoma multiforme (GBM) patients; however, its effect on the normal brain tissue remains unclear. Here, we investigated the short-term effects of multiple irradiation on the cellular and extracellular glycosylated components of normal brain tissue and their functional significance. Triple irradiation (7 Gy*3 days) of C57Bl/6 mouse brain inhibited the viability, proliferation and biosynthetic activity of normal glial cells, resulting in a fast brain-zone-dependent deregulation of the expression of proteoglycans (PGs) (decorin, biglycan, versican, brevican and CD44). Complex time-point-specific (24–72 h) changes in decorin and brevican protein and chondroitin sulfate (CS) and heparan sulfate (HS) content suggested deterioration of the PGs glycosylation in irradiated brain tissue, while the transcriptional activity of HS-biosynthetic system remained unchanged. The primary glial cultures and organotypic slices from triple-irradiated brain tissue were more susceptible to GBM U87 cells’ adhesion and proliferation in co-culture systems in vitro and ex vivo. In summary, multiple irradiation affects glycosylated components of normal brain extracellular matrix (ECM) through inhibition of the functional activity of normal glial cells. The changed content and pattern of PGs and GAGs in irradiated brain tissues are accompanied by the increased adhesion and proliferation of GBM cells, suggesting a novel molecular mechanism of negative side-effects of anti-GBM radiotherapy.

【 授权许可】

Unknown