Figure 1.

Mechanism of lung cancer brain metastasis. The changes of tumor microenvironment may promote some tumor cells to undergo epithelial-mesenchymal transition (EMT) process, to get the potential of metastasis and avoid apoptosis. These tumor cells escape from the primary tumor in the lung, invade the vessels, and circulate through the vessels, called circulating tumor cells (CTCs). Under the action of chemokines, CTCs reach the brain, cross the blood-brain barrier through rolling, adhesion and extravasation under the effect of E-ligand and integrin, undergo mesenchymal-epithelial transformation (MET) to regain the characteristic of the primary tumor, recover the characteristics of the primary tumor, and produce and adapt to the new tumor microenvironment. Angiogenesis is required for the growth of metastases. When pure oxygen diffusion is not sufficient for the tumor, the tumor gradually develops a hypoxic microenvironment and overexpress angiogenesis-stimulating factors, promoting the angiogenesis. The brain metastasis often happens in the gray and white matter junction and vascular border zones, where there is a longer mean transit times (MTT)of blood flow, providing more chance to overcome the blood-brain barrier.