Abstract
BackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-015-0257-2) contains supplementary material, which is available to authorized users.
Highlights
The central nervous system (CNS) is protected by several barriers, including the blood–brain (BBB) and blood-cerebrospinal fluid (BCSFB) barriers
IMR32 and SH‐SY5Y cells can cross the intact human in vitro blood-cerebrospinal fluid barrier (BCSFB) within 24 h and do not affect its overall integrity The transmigration of neuroblastoma cell lines was studied through the human BCSFB in vitro (Fig. 1), which consists of polarized human choroid plexus papilloma cells (HIBCPP) cells [6]
Between 0.14 and 0.22 % of neuroblastoma cells effectively transmigrated through the barrier and no significant difference could be seen between IMR32 and SH-SY5Y cell lines (Fig. 1b; 0.14 ± 0.02 and 0.22 ± 0.05 %, respectively)
Summary
The central nervous system (CNS) is protected by several barriers, including the blood–brain (BBB) and blood-cerebrospinal fluid (BCSFB) barriers. The blood–brain barrier (BBB) lies in the restrictive microvascular walls, whereas the blood-cerebrospinal fluid barrier (BCSFB) is formed by the choroid plexus epithelial cells [3]. Many studies have focused on the migration of cancer cells through the blood–brain barrier, whereas the BCSFB is underestimated as a potential route to reach the CNS. Our aim was to elucidate the migratory potential of neuroblastoma cells to cross the intact BCSFB. For this purpose, we studied the transmigration of two neuroblastoma cell lines—IMR32 and SH-SY5Y cells—through a well-established human in vitro BCSFB model. Our results show that these neuroblastoma cell lines could actively cross the choroid plexus epithelium within 24 h to a similar extent, and that the interactions with cancer cells did not cause a breakdown of the cellular barrier
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