Figure 3.

Fate of extravasated tumor cells in the brain microenvironment. After migration through the vessel wall, large part of metastatic cells dies in the brain microenvironment. Astrocyte-released PA is involved in killing serpin-negative tumor cells. Surviving cells either remain dormant, closely attached to the vessel wall or start proliferating in response to signals arising from the brain microenvironment. Strong reactive astrocytosis persists during growth of the metastatic lesion. Astrocytes support proliferation of malignant cells through release of soluble factors and exososmes and formation of heterocellular gap junctions. Astrocyte-dependent Notch signaling is involved in the maintenance of the CSC phenotype in brain metastatic breast cancer cells. Response of microglial cells to cancer cells is heterogeneous. Increased secretion of cathepsin S and release of chemokines from microglia might promote viability and migration of tumor cells in the brain. GJ: gap junction.