Table 1.
Major ECMs in GBM and brain parenchyma (excluding BBB)
| ECM | Class | Structure | Size | Primary crosstalk | Expression in GBM stroma | Primary functions in brain and GBM | Ref. |
|---|---|---|---|---|---|---|---|
| HA | GAG | Linear polysaccharide with no protein core | >1,000 kDa in normal brain | Integrins, CD44, RHAMM, lectican, GHAP | Increased, low molecular weight forms present | GBM progression and invasion; structural and biochemical support to brain | [39,60,63,148] |
| TSP-1 | MCP | Homotrimer with three type 1 repeats | 420 kDa | Heparin, α5β1 integrin, HSPG, fibronectin, laminin | Decreased | GBM cell adhesion, migration, invasion; MMP inhibition; angiogenesis inhibition | [39] |
| TN-C | MCP | Oligomer with six monomers linked by disulfide bonds | 180–250 kDa (each monomer) | Lectican, HSPG, fibronectin, α5β1/αvβ6 integrins, CAM, phosphacan | Increased | Angiogenesis; ECM stiffness; immune suppression; EMT; GBM migration | [39,65,70,72,193] |
| TN-R | MCP | Present in monomeric, dimeric, or trimeric forms | 160 or 180 kDa (each monomer) | Lectican, fibronectin | Decreased | Brain plasticity regulation; synaptic activity stablization | [64,65,73] |
| SPARC | MCP | Trimer | 32 kDa | Collagen, vitronectin | Increased | Cell de-adhesion; tissue remodeling; angiogenesis; EMT | [39,70,194] |
| Osteopontin | MCP | Phosphorylated protein | 60kDa | CD44, integrin, heparin | Increased | Angiogenesis; GSC stemness; tumor growth and invasion | [74] |
| Lectican | CSPG | (See subclass) | 95–400 kDa | HA, TN-R, fibulin-2 | (See subclass) | (See subclass) | [56,59,64] |
| Subclass | Structure | Expression in GBM stroma | Primary functions in brain and GBM | Ref. | |||
| Aggrecan | G1, G2, and G3 domains with a center domain for CS/KS chains | - | Brain plasticity regulation | [195] | |||
| Versican | Two subdomains GAGα and GAGβ, and a central domain binds CS chains. Isoform V0 carries both; V1 with only GAGβ; V2 with only GAGα; V3 lacks both. | V0/V1 increase V2 decrease |
Cell adhesion and migration; drug resistance | [60,70] | |||
| Brevican | N- and C-terminal domains and a center domain for CS chains. | Significantly increased | GBM growth and progression | [69,196] | |||
| Neurocan | N- and C-terminal domains and a center domain binds up to 7 CS chains. | - | Inhibition of neurite outgrowth | [195] | |||