Table 1.
Vessel co-option pathways in GBMs
| Pathways | Experimental model | Notes | References |
|---|---|---|---|
| Bradykinin | Patient-derived D54 in vivo model and in vitro co-culture | Bradykinin is released from blood vessels, while GBM cells express B2R, their inhibition impairs vessel co-option | [34, 35] |
| CXCR4/SDF1α | Gl261 mouse in vivo model and in vitro co-culture | SDF1α is expressed in neuronal and endothelial cells, while GBM cells express CXCR4, their inhibition impairs vessel co-option and radiosensitizes tumors | [33, 37–39] |
| Ang-2 | C6 rat in vivo model | Ang-2 and VEGF are expressed in vessel co-option areas as a consequence of vascular regression | [33, 43] |
| IL-8 | In vitro co-culture and in vivo implants | Endothelial cells increase GBM invasiveness and tumor growth through IL-8-mediated enrichment of glioma stem cells | [46, 47] |
| EGFRvIII | Mouse in vivo model and ex vivo brain slice | EGFRvIII-hi GBM cells are highly vessel co-opting and tumors originated by them are highly infiltrative and aggressive | [49] |
| MDGI/FABP3 | Mouse in vivo model and ex vivo brain slice | Modulation of MDGI/FABP3 strongly alters the GBM cells’ ability of infiltrating the surrounding brain tissue with perivascular migration | [51, 52] |
| IRE-1α | Neurospheres and U87 in vivo models | Inhibition of IRE-1α increases vessel co-option and decreases pro-angiogenic pathways | [54, 55] |
| CDC42 | Ex vivo brain slice | Vessel co-opting GBM cells co-opt and interact with pericytes in a CDC42-dependent manner | [30] |
| EphrinB2 | Patient-derived MGG8 in vivo model, syngeneic model and in vitro co-culture | Endothelial Ephrin-B2 regulates vessel co-option, when, and only if, the ligand Ephrin-B2 is upregulated in GBM cells | [58] |
| Olig2/Wnt7a | Patient-derived MGG8 in vivo model, EGFRvIII-induced syngeneic model and ex vivo brain slice | Olig2-Wnt7 axis drives individual vessel co-option in oligodendrocyte-like GBM cells, its inhibition impairs vessel co-option and chemosensitizes tumors | [18, 25] |
CXCR4 CXC receptor-4, SDF1α stromal cell-derived factor-1α, IL-8 interleukin 8, Ang-2 angiopoietin 2, CDC42 cell division control protein 42, EGFRvIII epidermal growth factor receptor variant III, MDGI/FABP3 mammary-derived growth inhibitor (MDGI)/fatty acid binding protein 3, IRE1α inositol-requiring enzyme (IRE)-1α, Wnt is acronym of homologous wingless (wg) and Int-1, Olig2 oligodendrocyte transcription factor