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Multiple Irradiation Affects Cellular and Extracellular Components of the Mouse Brain Tissue and Adhesion and Proliferation of Glioblastoma Cells in Experimental System In Vivo.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Dec 12; Vol. 22 (24). Date of Electronic Publication: 2021 Dec 12. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Animals
Cell Adhesion radiation effects
Extracellular Matrix Proteins metabolism
Male
Mice
Proteoglycans metabolism
Brain metabolism
Brain pathology
Brain Neoplasms metabolism
Brain Neoplasms pathology
Brain Neoplasms radiotherapy
Cell Proliferation radiation effects
Gamma Rays
Glioblastoma metabolism
Glioblastoma pathology
Glioblastoma radiotherapy
Neoplasms, Experimental metabolism
Neoplasms, Experimental pathology
Neoplasms, Experimental radiotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34948147
- Full Text :
- https://doi.org/10.3390/ijms222413350