Fucosyltransferase 4 and 7 mediates adhesion of non-small cell lung cancer cells to brain-derived endothelial cells and results in modification of the blood–brain-barrier: in vitro investigation of CD15 and CD15s in lung-to-brain metastasis

• DOI: 10.1007/s11060-019-03188-x
• Publication Date: 2019-05-19T06:22:29Z
• Authors: Samah A. Jassam; Zaynah Maherally; Keyoumars Ashkan; Geoffrey J. Pilki...; Helen L. Fillmore
• Keywords: 0303 health sciences; Lung Neoplasms; Brain Neoplasms; FUT7; Biomedical Sciences; Endothelial Cells; Lewis X Antigen; FUT4; NSCLC; Fucosyltransferases; 3. Good health; 03 medical and health sciences; Blood-Brain Barrier; Cell Movement; Carcinoma, Non-Small-Cell Lung; /dk/atira/pure/core/subjects/biomedicalsciences; Laboratory Investigation; Cell Adhesion; Tumor Cells, Cultured; CD15s; Humans; brain metastasis; CD15

Metastatic non-small cell lung (NSCLC) cancer represents one of the most common types brain metastasis. The mechanisms involved in how circulating cells transmigrate into parenchyma are not fully understood. aim this work was to investigate role fucosylated carbohydrate epitopes CD15 and sialyated CD15s adhesion brain-derived endothelial determine their influence blood-brain barrier (BBB) disruption METHODS: Three distinct, independent methods were used measure integrity include voltohmmeter (EVOM™), impedance spectroscopy (CellZscope®) electric cell-substrate sensing system (ECIS™). Two fucosyltransferases (FUT4 7) responsible for synthesis modulated four human lines (three glioma).Overexpression or led increase cerebral compared with wild-type silenced (p < 0.01). This overexpression monolayers Knockdown FUT4 FUT7 metastatic prevented an vitro BBB model. Surprisingly, although characterised as 'non-metastatic', they became 'metastatic' -like when forced over-express either FUT7.Results from these studies suggest that could potentiate transmigration NSCLC brain. clinical significance includes possible use biomarkers