Figure 4.

Key steps of the breast-to-brain metastatic process. (Step 1) Adhesion of the metastatic circulating breast cancer cells to the brain microvascular endothelial cells; (Step 2) BBB passage of metastatic cells leaving the circulation by transendothelial migration; (Step 3) adaptation and proliferation of the metastatic cells in their new perivascular niche; (Step 4) establishment of the tumor microenvironment with metastatic breast cancer cells interacting with the key NVU cellular partner pericytes, astrocytes, and microglia. Astrocyte foot processes associated with the parenchymal basal lamina form the outermost layer of central nervous tissue known as glia limitans.