Table 6.
The Janus-faced attitude of cells of the NVU towards metastatic cells.
| NVU cell | Anti-tumor mechanism | Tumor protective mechanism | References |
|---|---|---|---|
| CECs | Form a barrier for extravasating tumor cells | ||
| Facilitate transmigration of tumor cells (COX-2 activation, MMP-2 release) | 122 | ||
| Provide chemoprotection through gap junction communication and endothelin signaling | 130 | ||
| Provide chemoprotection through efflux transporters | 132,133 | ||
| Provide shielding against cytotoxic immune cells | |||
| Astrocytes | Secrete plasminogen which activates plasmin to cleave FasL (to kill cancer cells) and L1CAM (to block vessel cooption) | 134 | |
| Release exosomes containing miR-19a which activates the PI3K/Akt survival pathway | 151 | ||
| Secrete proteases, growth factors and inflammatory cytokines which favor growth of tumor cells | 58,75,101,155,229–231 | ||
| Promote self-renewal of breast CSCs through the JAG1-Notch-signaling pathway | 152 | ||
| Form gap junctions with tumor cells, leading to sequestration of excess of Ca2+, upregulation of survival genes, secretion of inflammatory cytokines, activation of PI3K signaling | 130,155,156,158 | ||
| Microglia | May secrete factors which inhibit tumor cell proliferation | 162,163 | |
| Secrete cathepsin S to promote brain metastasis formation | 92 | ||
| Secrete CCL22 and CCL17 promoting viability of melanoma cells | 74 |
NVU: neurovascular unit; CEC: cerebral endothelial cell; CSC: cancer stem-like cell.