Fig. 6

Schematic illustration showing transmigration of metastatic cells through the BAB into the subarachnoid space. Some metastatic cells, such as ALL lymphocytes, use α6 integrin to bind to laminin. After metastatic cells migrate to the meninges, surrounding immune cells release pro-inflammatory cytokines and recruit cytotoxic T cells. Later, metastatic cells begin to induce an immunosuppressive microenvironment including regulatory T cells (Tregs) and inhibitory macrophages. To reach the cerebrospinal fluid, metastatic cells must pass through the epithelial cells of the BAB, which are connected by TJ proteins. Metastatic cells in the subarachnoid space produce proteases such as MMP-2 and MMP-9 that degrade the pial-glial membrane containing type IV collagen and enter the brain tissue