Table 1.
Radiation-induced alterations to the GBM micro-environment.
| Biological process | Consequence | RT-effect | References |
|---|---|---|---|
| EXTRACELLULAR MATRIX COMPOSITION AND BIOSYNTHESIS | |||
| Collagen | Migration and Invasion | +/Up | (38, 45, 46) |
| Tenascin C | Tumor proliferation, Invasion | +/Up | (28, 29, 47) |
| Hyaluronin | Invasion | +/Up | (48, 49) |
| Brevican | Migration, Invasion | +/Up | (25, 30, 50) |
| Vitronectin | Survival, Migration, Inflammation | +/Up | (26) |
| MDA-9/Syntenin | Metastasis, tumor progression | +/Up | (51) |
| LOX | Migration | +/Up | (52) |
| ECM-GLIOMA CELL (LIGAND-RECEPTOR) INTERACTION | |||
| DDR-1, ICAM-1, α5β1, αvβ3 | Migration, Invasion | +/Up | (31, 53–55) |
| ECM DEGRADATION | |||
| MMPs | Invasion | +/Up | (56–59) |
| TIMP | Angiogenesis, Metastasis | +/Up | (60, 61) |
| TUMOR CELL ADAPTATION MECHANISMS | |||
| Oxygen tension: HIF-1 | Hypoxia, malignancy | +/Up | (62) |
| Metabolism: ATP, NAD | Proliferation | +/Up | (63) |
| Anti-apoptosis: BCL2/BAX | Migration, invasiveness | +/Up | (55) |
| Redox regulation (ROS/RNS, NOX4) | Senescence, inflammation | +/Up | (64–66) |
| Angiogenesis (VEGF, Ang) | Angiogenesis | +/Up | (67) |
| Inflammation (Cytokines, Chemokines, Chemokine receptors) | Tumor proliferation, migration, invasion | +/Up | (68–72) |
| Glia activation (MHC, CD68, GFAP) | proliferation | +/Up | (70, 73–75) |
| Neurogenesis (NSC) | Cognitive decline | -/Impaired | (76) |
MDA-9, Melanoma differentiation-associated gene-9; LOX, Lysl oxidase; DDR-1, Discoidin domain receptor-1; ICAM-1, Intercellular Adhesion Molecule 1; Integrins α5β1; Integrin, αvβ3; MMPs, Matrix metalloproteinases; TIMP, Tissue inhibitor of matrix metalloproteinase; NSC, Neural stem cell; HIF-1, Hypoxia-inducible factor 1; VEGF, Vascular endothelial growth factor; Ang, Angiotensins; CALR, Calreticulin; HGMB1, High mobility group box 1 protein; NOX4, NADPH oxidase 4; ROS, Reactive oxygen species; RNS, Reactive nitrogen species; MHC, Major histocompatibility complex; ATP, Adenosine triphosphate; GFAP, Glial acidic fibrillary protein; NAD, Nicotinamide adenine dinucleotide; CD, Cluster of differentiation; BCL2, B-cell lymphoma-2; BAX, BCL2 Associated X. Cytokines: Tumor necrosis factor-α, TNF- α; Transforming growth factor-β, TGF-β, IL, Interleukins (IL-6, IL-8, IL-1β). Chemokines: CX3C family (CX3CL1, Fractalkine), CCL family (CCL2, CCR3, CCL7, CCL8, CCL12), CXC family (CXCL4, CXCL12/stromal cell-derived factor 1, SDF1). Chemokine receptors: CC-chemokine receptor family (CCR1, CCR2). RT-effects: +, positive; Up-upregulation/increased; –, negative.