![]() The BBB is a dynamic and selective defensive barrier, which maintains a highly specific environment within the CNS by inhibiting both fluctuations of plasma components and entry of substances that may potentially cause brain toxicity. The central nervous system (CNS) is considered a site of refuge as cancers are protected from most systemic therapies by the blood–brain barrier (BBB). As overall survival in patients with primary non-CNS cancers has improved, the incidence of metastasis to the brain has also increased, possibly due to circulating cancer cells which persist despite patient remission. The highest incidence of brain metastasis is seen in lung cancer patients (40–50%) followed by breast (20–30%) and melanoma (5–10%). 20–40% of patients with systemic cancers develop secondary brain tumours. The majority of intracranial tumours are secondary metastases originating from primary non-central nervous system (non-CNS) cancers. The clinical significance of these studies includes the possible use of these epitopes as biomarkers for metastasis. Results from these studies suggest that overexpression of CD15 and CD15s could potentiate the transmigration of circulating NSCLC cells into the brain. Surprisingly, although the cells characterised as ‘non-metastatic’, they became ‘metastatic’ -like when cells were forced to over-express either FUT4 or FUT7. Knockdown of FUT4 and FUT7 in metastatic cancer cells prevented disruption of an in vitro BBB model. This overexpression led to the disruption of cerebral endothelial cell monolayers (p < 0.01). Overexpression of CD15 or CD15s epitopes led to increase in adhesion of cancer cells to cerebral endothelial cells compared with wild-type and cells with silenced CD15 or CD15s (p < 0.01). Two fucosyltransferases (FUT4 and 7) responsible for CD15 and CD15s synthesis were modulated in four human cancer cell lines (three lung cancer and one glioma). Three distinct, independent methods were used to measure brain endothelial integrity and include voltohmmeter (EVOM™), impedance spectroscopy (CellZscope®) and electric cell-substrate impedance sensing system (ECIS™). ![]() The aim of this work was to investigate the role of fucosylated carbohydrate epitopes CD15 and sialyated CD15s in cancer adhesion to brain-derived endothelial cells and determine their influence in blood–brain barrier (BBB) disruption Methods The mechanisms involved in how circulating cancer cells transmigrate into brain parenchyma are not fully understood. Metastatic non-small cell lung (NSCLC) cancer represents one of the most common types of brain metastasis.
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