The Stem Cell Marker Prominin-1/CD133 on Membrane Particles in Human Cerebrospinal Fluid Offers Novel Approaches for Studying Central Nervous System Disease

Author:

Huttner Hagen B.123,Janich Peggy2,Köhrmann Martin1,Jászai József2,Siebzehnrubl Florian4,Blümcke Ingmar4,Suttorp Meinolf5,Gahr Manfred5,Kuhnt Daniela6,Nimsky Christopher6,Krex Dietmar7,Schackert Gabriele7,Löwenbrück Kai8,Reichmann Heinz8,Jüttler Eric3,Hacke Werner3,Schellinger Peter D.1,Schwab Stefan1,Wilsch-Bräuninger Michaela9,Marzesco Anne-Marie9,Corbeil Denis2

Affiliation:

1. Department of Neurology, University of Erlangen, Erlangen, Germany

2. Tissue Engineering Laboratories (Biotec), University of Dresden, Dresden, Germany

3. Department of Neurology, University of Heidelberg, Heidelberg, Germany

4. Department of Neuropathology, University of Erlangen, Erlangen, Germany

5. Department of Pediatrics, University of Dresden, Dresden, Germany

6. Department of Neurosurgery, University of Erlangen, Erlangen, Germany

7. Department of Neurosurgery, University of Dresden, Dresden, Germany

8. Department of Neurology, University of Dresden, Dresden, Germany

9. Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany

Abstract

Abstract Cerebrospinal fluid (CSF) is routinely used for diagnosing and monitoring neurological diseases. The CSF proteins used so far for diagnostic purposes (except for those associated with whole cells) are soluble. Here, we show that human CSF contains specific membrane particles that carry prominin-1/CD133, a neural stem cell marker implicated in brain tumors, notably glioblastoma. Differential and equilibrium centrifugation and detergent solubility analyses showed that these membrane particles were similar in physical properties and microdomain organization to small membrane vesicles previously shown to be released from neural stem cells in the mouse embryo. The levels of membrane particle-associated prominin-1/CD133 declined during childhood and remained constant thereafter, with a remarkably narrow range in healthy adults. Glioblastoma patients showed elevated levels of membrane particle-associated prominin-1/CD133, which decreased dramatically in the final stage of the disease. Hence, analysis of CSF for membrane particles carrying the somatic stem cell marker prominin-1/CD133 offers a novel approach for studying human central nervous system disease. Disclosure of potential conflicts of interest is found at the end of this article.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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