Fig. 2

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms. Tumor cells and exosomes originating from primary tumors can disrupt the BBB (blood–brain barrier) via their contents. Exosomes carry microRNAs (such as miR-105 and miR-181c), whose involvement leads to increased permeability of the blood–brain barrier (BBB). LncRNA GS1-600G8.5 lowers the expression of ZO-1, Claudin-5, and N-Cadherin. Lnc-Matrix metallopeptidases (MMP)2–2, as part of the exosomal cargo, also disrupt tight junctions, thereby increasing the permeability of the BBB. This promotes intracranial metastasis of tumor cells. Exosomes interact with microglia in the brain and help establish pre-metastatic niches. Furthermore, exosomes promote the proliferation of the BM (brain metastases), alter the immune microenvironment, regulate the stability of tumor cells, and can be used as diagnostic and prognostic biomarkers