Figure 1.

Establishment of brain metastases. (A) Mechanisms of tumor cell invasion, intravasation, survival in circulation, extravasation, and tissue colonization. (B) Mechanisms associated to the pre-metastatic niche including factors such as VEGF, PLGF, and MMP (matrix metalloproteinases). (B) Tumor-secreted exosomes containing nucleic acids such as miRNAs and lncRNAs, as well as proteins and lipids. (C) Contributing factors that increase permeability of the BBB including alterations in channel transporters, loss of tight junctions, and collagen produced by pericytes. (D) The BBB breakdown and the establishment of the BTB reflected by tumor cell extravasation into the brain parenchyma.