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The impact of small extracellular vesicles on lymphoblast trafficking across the blood-cerebrospinal fluid barrier in vitro

Central nervous System (CNS) disease in pediatric acute lymphoblastic leukemia (ALL) is a major concern, but still, cellular mechanisms of CNS infiltration are elusive. The choroid plexus (CP) is a potential entry site, and, to some extent, invasion resembles CNS homing of lymphocytes during healthy...

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Hauptverfasser: Erb, Ulrike (Verfasst von) , Hikel, Julia (Verfasst von) , Meyer, Svenja (Verfasst von) , Ishikawa, Hiroshi (Verfasst von) , Worst, Thomas (Verfasst von) , Nitschke, Katja (Verfasst von) , Nuhn, Philipp (Verfasst von) , Porubský, Štefan (Verfasst von) , Weiß, Christel (Verfasst von) , Schroten, Horst (Verfasst von) , Adam, Rüdiger (Verfasst von) , Karremann, Michael (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 31 July 2020
In: International journal of molecular sciences
Year: 2020, Jahrgang: 21, Heft: 15, Pages: 1-14
ISSN:1422-0067
DOI:10.3390/ijms21155491
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms21155491
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/21/15/5491
Volltext
Verfasserangaben:Ulrike Erb, Julia Hikel, Svenja Meyer, Hiroshi Ishikawa, Thomas S. Worst, Katja Nitschke, Philipp Nuhn, Stefan Porubsky, Christel Weiss, Horst Schroten, Rüdiger Adam, and Michael Karremann
Beschreibung
Zusammenfassung:Central nervous System (CNS) disease in pediatric acute lymphoblastic leukemia (ALL) is a major concern, but still, cellular mechanisms of CNS infiltration are elusive. The choroid plexus (CP) is a potential entry site, and, to some extent, invasion resembles CNS homing of lymphocytes during healthy state. Given exosomes may precondition target tissue, the present work aims to investigate if leukemia-derived exosomes contribute to a permissive phenotype of the blood-cerebrospinal fluid barrier (BCSFB). Leukemia-derived exosomes were isolated by ultracentrifugation from the cell lines SD-1, Nalm-6, and P12-Ichikawa (P12). Adhesion and uptake to CP epithelial cells and the significance on subsequent ALL transmigration across the barrier was studied in a human BCSFB in vitro model based on the HiBCPP cell line. The various cell lines markedly differed regarding exosome uptake to HiBCPP and biological significance. SD-1-derived exosomes associated to target cells unspecifically without detectable cellular effects. Whereas Nalm-6 and P12-derived exosomes incorporated by dynamin-dependent endocytosis, uptake in the latter could be diminished by integrin blocking. In addition, only P12-derived exosomes led to facilitated transmigration of the parental leukemia cells. In conclusion, we provide evidence that, to a varying extent, leukemia-derived exosomes may facilitate CNS invasion of ALL across the BCSFB without destruction of the barrier integrity.
Beschreibung:Gesehen am 10.08.2026
Beschreibung:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms21155491

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