Radiation Effects on Brain Extracellular Matrix

Abstract

Radiotherapy is an important therapeutic approach to treating malignant tumors of different localization, including brain cancer. Glioblastoma multiforme (GBM) represents the most aggressive brain tumor, which develops relapsed disease during the 1st year after the surgical removal of the primary node, in spite of active adjuvant radiochemotherapy. More and more evidence suggests that the treatment's success might be determined by the balance of expected antitumor effects of the treatment and its non-targeted side effects on the surrounding brain tissue. Radiation-induced damage of the GBM microenvironment might create tumor-susceptible niche facilitating proliferation and invasion of the residual glioma cells and the disease relapse. Understanding of molecular mechanisms of radiation-induced changes in brain ECM might help to reconsider and improve conventional anti-glioblastoma radiotherapy, taking into account the balance between its antitumor and ECM-destructing activities. Although little is currently known about the radiation-induced changes in brain ECM, this review summarizes current knowledge about irradiation effects onto the main components of brain ECM such as proteoglycans, glycosaminoglycans, glycoproteins, and the enzymes responsible for their modification and degradation.

Keywords: brain irradiation; chondroitin sulfate; extracellular matrix; glioblastoma radiotherapy; heparan sulfate; heparanase; metalloproteinase; proteoglycan expression.

Figure 1

Schematic illustration of irradiation-induced changes in the expression of various ECM components in glioma cells/tumors and normal brain tissue. The genes, which expression changes were shown at least in a single study, are depicted on the scheme. Arrows correspond to up-regulation (↗) or down-regulation (↘) of the gene expression.