The choroid plexus may be an underestimated site of tumor invasion to the brain: an in vitro study using neuroblastoma cell lines.
The central nervous system (CNS) is protected by several barriers, including the blood-brain (BBB) and blood-cerebrospinal fluid (BCSFB) barriers. Understanding how cancer cells circumvent these protective barriers to invade the CNS is of crucial interest, since brain metastasis during cancer is often a fatal event in both children and adults. However, whereas much effort has been invested in elucidating the process of tumor cell transmigration across the BBB, the role of the BCSFB might still be underestimated considering the significant number of meningeal cancer involvement. Our work aimed to investigate the transmigration of neuroblastoma cells across the BCSFB in vitro.



We used an inverted model of the human BCSFB presenting proper restrictive features including adequate expression of tight-junction proteins, low permeability to integrity markers, and high trans-epithelial electrical resistance. Two different human neuroblastoma cell lines (SH-SY5Y and IMR-32) were used to study the transmigration process by fluorescent microscopy analysis.



The results show that neuroblastoma cells are able to actively cross the tight human in vitro BCSFB model within 24 h. The presence and transmigration of neuroblastoma cancer cells did not affect the barrier integrity within the duration of the experiment.



In conclusion, we presume that the choroid plexus might be an underestimated site of CNS invasion, since neuroblastoma cell lines are able to actively cross a choroid plexus epithelial cell layer. Further studies are warranted to elucidate the molecular mechanisms of tumor cell transmigration in vitro and in vivo.
Laboratoire de la Barrière Hémato-Encéphalique (LBHE), EA 2465, Université d'Artois (UArtois), Lens, France.
Elodie
E
Vandenhaute
Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Carolin
C
Stump-Guthier
Institute of Experimental Medicine I, Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
María
M
Lasierra Losada
Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Tobias
T
Tenenbaum
Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Henriette
H
Rudolph
Department of NDU Life Sciences, School of Life Dentistry, The Nippon Dental University, Tokyo, Japan.
Hiroshi
H
Ishikawa
Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Christian
C
Schwerk
Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Horst
H
Schroten
Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Matthias
M
Dürken
Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Martin
M
März
Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Michael
M
Karremann
Blood-cerebrospinal fluid barrier; Brain metastases; Cancer cell transmigration; Choroid plexus; In vitro model; Neuroblastoma