title: Selection of a Relevant In Vitro Blood-Brain Barrier Model to Investigate Pro-Metastatic Features of Human Breast Cancer Cell Lines.
abstract: Around 7-17% of metastatic breast cancer patients will develop brain metastases, associated with a poor prognosis. To reach the brain parenchyma, cancer cells need to cross the highly restrictive endothelium of the Blood-Brain Barrier (BBB). As treatments for brain metastases are mostly inefficient, preventing cancer cells to reach the brain could provide a relevant and important strategy. For that purpose an in vitro approach is required to identify cellular and molecular interaction mechanisms between breast cancer cells and BBB endothelium, notably at the early steps of the interaction. However, while numerous studies are performed with in vitro models, the heterogeneity and the quality of BBB models used is a limitation to the extrapolation of the obtained results to in vivo context, showing that the choice of a model that fulfills the biological BBB characteristics is essential. Therefore, we compared pre-established and currently used in vitro models from different origins (bovine, mice, human) in order to define the most appropriate tool to study interactions between breast cancer cells and the BBB. On each model, the BBB properties and the adhesion capacities of breast cancer cell lines were evaluated. As endothelial cells represent the physical restriction site of the BBB, all the models consisted of endothelial cells from animal or human origins. Among these models, only the in vitro BBB model derived from human stem cells both displayed BBB properties and allowed measurement of meaningful different interaction capacities of the cancer cell lines. Importantly, the measured adhesion and transmigration were found to be in accordance with the cancer cell lines molecular subtypes. In addition, at a molecular level, the inhibition of ganglioside biosynthesis highlights the potential role of glycosylation in breast cancer cells adhesion capacities.
authors.affiliation: Université d'Artois (UArtois), EA2465, LBHE, Lens, F-62307, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Drolez
authors.affiliation: Université d'Artois (UArtois), EA2465, LBHE, Lens, F-62307, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Vandenhaute
authors.affiliation: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University of Lille, Villeneuve d'Ascq, France.|Cell Plasticity and Cancer, U908 INSERM, University of Lille, Villeneuve d'Ascq, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Julien
authors.affiliation: Université d'Artois (UArtois), EA2465, LBHE, Lens, F-62307, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gosselet
authors.affiliation: Research Oncology, King's College London, London, SE1 9RT, United Kingdom.
authors.forename: Joy
authors.initials: J
authors.lastname: Burchell
authors.affiliation: Université d'Artois (UArtois), EA2465, LBHE, Lens, F-62307, France.
authors.forename: Roméo
authors.initials: R
authors.lastname: Cecchelli
authors.affiliation: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University of Lille, Villeneuve d'Ascq, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delannoy
authors.affiliation: Université d'Artois (UArtois), EA2465, LBHE, Lens, F-62307, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dehouck
authors.affiliation: Université d'Artois (UArtois), EA2465, LBHE, Lens, F-62307, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mysiorek
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology*; D002417:Cattle; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D051381:Rats
chemical_list: D018952:Antigens, CD34