Fig. 4

Mechanisms of Metastatic Cell Rolling and Adhesion to Brain Endothelial Cells. This schematic illustrates the endothelial cell layer, pericytes, and astrocytes forming the blood–brain barrier, with metastatic cells depicted in the process of adhering to endothelial cells facilitated by various molecular interactions. Rolling phase: Endothelial cells express E-selectin, which binds to glycoproteins such as HCELL, CD24, PSGL-1, and CEA on the surface of metastatic cells, initiating the rolling process. The adhesion phase includes the following steps: (1) Leukocyte bridging: Metastatic cells use leukocytes (which express β2 integrins) as intermediaries to bind to ICAM-1 on endothelial cells. (2) Direct adhesion: Metastatic cells also express integrins (α4, β1, β7) that interact with VCAM-1 on endothelial cells, facilitating direct adhesion. Additionally, MUC1, CD44v6, and lysosomal-associated membrane proteins (Lamps) 1 and 2 on metastatic cells bind to galectin-3 on endothelial cells, enhancing adhesion. 3) N-cadherin interaction: N-cadherin on metastatic cells interacts with N-cadherin on brain endothelial cells, promoting stable cell contact