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Aberrant immunostaining pattern of the CD24 glycoprotein in clinical samples and experimental models of pediatric medulloblastomas

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Abstract

The CD24 glycoprotein is a mediator of neuronal proliferation, differentiation and immune suppression in the normal CNS, and a proposed cancer biomarker in multiple peripheral tumor types. We performed a comparative analysis of CD24 gene expression in a large cohort of pediatric and adult brain tumors (n = 813), and further characterized protein expression in tissue sections (n = 39), primary brain tumor cultures (n = 12) and a novel orthotopic group 3 medulloblastoma xenograft model. Increased CD24 gene expression was demonstrated in ependymomas, medulloblastomas, anaplastic astrocytomas and glioblastomas, although medulloblastomas displayed higher expression than all other tumor entities. Preferential expression of CD24 in medulloblastomas was confirmed at protein level by immunostaining and computerized image analysis of cryosections. Morphologies and immunophenotyping of CD24+ cells in tissue sections tentatively suggested disparate functions in different tumor subsets. Notably, protein staining of medulloblastoma cells was associated with prominent cytoplasmic and membranous granules, enabling rapid and robust identification of medulloblastoma cells in clinical tissue samples, as well as in experimental model systems. In conclusion, our results implicate CD24 as a clinically and experimentally useful medulloblastoma immunomarker. Although our results encourage further functional studies of CD24 as a potential molecular target in subsets of brain tumors, the promiscuous expression of CD24 in vivo highlights the importance of specificity in the future design of such targeted treatment.

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Acknowledgments

This study was supported by the Swedish Childhood Cancer Foundation, the Network for Neuroblastoma and CNS tumor research in children (NBCNS), the Skåne University Hospital donation funds, the Governmental funding of clinical research within the national health services (ALF), the Royal Physiographic Society in Lund, the Swedish Society of Medicine, the Crafoord Foundation and Jonasfonden. We thank Erika Bourseau-Guilman and Jonna Liljenberg for excellent technical support, and Charlotte Saltin for handling of tissue specimens during surgery.

Conflict of interest

All authors declare no conflict of interest.

Compliance with ethical standards

The Local Ethical Board of Lund University approved the collection and analyses of tumor samples at Lund University Hospital (LU1028-03, ETIK2008/642). All patients and/or their parents gave their informed consent prior to inclusion in the study. All animal experiments were approved by the regional ethics committee for animal research (N137/10), appointed and under the control of the Swedish Board of Agriculture and the Swedish Court. The animal experiments presented herein were in accordance with national regulations (SFS 1988:534, SFS 1988:539, and SFS 1988:541).

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Authors and Affiliations

  1. Glioma Immunotherapy Group, Division of Neurosurgery, Department of Clinical Sciences Lund, Lund University, Barngatan 2B, 221 85, Lund, Sweden

    Emma Sandén, Edward Visse, Peter Siesjö & Anna Darabi

  2. Childhood Cancer Research Unit, Department of Women´s and Children´s Health, Karolinska Institutet, Stockholm, Sweden

    Cecilia Dyberg, Cecilia Krona & John I. Johnsen

  3. Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

    Helena Carén

  4. Division of Pediatric Neurooncology, German Cancer Research Center DKFZ, Heidelberg, Germany

    Paul A. Northcott & Marcel Kool

  5. Division of Neurosurgery, Department of Clinical Sciences Lund, Skåne University Hospital, Lund, Sweden

    Nils Ståhl & Peter Siesjö

  6. Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden

    Annette Persson & Elisabet Englund

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  1. Emma Sandén
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Correspondence to Emma Sandén.

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Sandén, E., Dyberg, C., Krona, C. et al. Aberrant immunostaining pattern of the CD24 glycoprotein in clinical samples and experimental models of pediatric medulloblastomas. J Neurooncol 123, 1–13 (2015). https://doi.org/10.1007/s11060-015-1758-5

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  • DOI: https://doi.org/10.1007/s11060-015-1758-5

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