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. 2023 Apr 12;15(8):2258. doi: 10.3390/cancers15082258

Figure 3.

Figure 3

Schematic representation of extravasation steps in lung cancer brain metastasis. (A) Rolling and firm adhesion: During adhesion to BE, lung cancer cells express ALCAM, CD15, CD15s (sLex), annexin A1 and ADAM9 that upregulate integrin α3β1 [35,130,134]. (B) Trans-endothelial migration: During TEM, BECs downregulate the expression of Mfsd2a to induce permeability of BBB. Downregulation of adenosine A2A receptor in lung cancer cells activate SDF-1/CXCR4 signaling pathway and inhibits the expression of claudin-5, occludin, and ZO-1 [136]. Upregulation of AKR1B10, degrades (ZO-1 and VE- cadherin) and increases the levels of MMP2 and MMP9 [137]. BE Rho/ROCK signaling facilitates TEM with subsequent disruption of (occludin, claudin-5, and ZO-1) [139]. PLGF disrupts occludin and ZO-1 through interacting with its receptor, VEGFR-1 [140]. Visfatin upregulates CCL2 to promote TEM [142]. Photo created with BioRender.com.