Fig. 2.

Pathogenesis of brain metastases. The development of brain metastases depends on a complex interplay of factors involving tumor cells migrating from an extracranial site into the vasculature via a series of epigenetic changes, proliferation of blood vessels, and an epithelial-to-mesenchymal transition. Once the tumor cells reach the brain, they traverse the blood brain barrier, which involves upregulation of genes and proteins involved in proteolysis, extracellular matrix destruction, and mitogenesis/growth. Once inside the brain, the cells must adhere to the brain endothelia and undergo further stimulatory processes to allow for proliferation.