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Capture and Detection of Circulating Glioma Cells Using the Recombinant VAR2CSA Malaria Protein

Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200 Copenhagen, Denmark
VarCT Diagnostics, 2200 Copenhagen, Denmark
Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
Department of Urologic Sciences, University of British Columbia, and Vancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada
Centre for Genomic Medicine, Copenhagen University Hospital, 2100 Copenhagen, Denmark
ExpreS2ion Biotechnologies, SCION-DTU Science Park, 2970 Hørsholm, Denmark
Department of Oncology, Copenhagen University Hospital, 2100 Copenhagen, Denmark
Authors to whom correspondence should be addressed.
Cells 2019, 8(9), 998;
Received: 8 July 2019 / Revised: 21 August 2019 / Accepted: 25 August 2019 / Published: 28 August 2019
Diffuse gliomas are the most common primary malignant brain tumor. Although extracranial metastases are rarely observed, recent studies have shown the presence of circulating tumor cells (CTCs) in the blood of glioma patients, confirming that a subset of tumor cells are capable of entering the circulation. The isolation and characterization of CTCs could provide a non-invasive method for repeated analysis of the mutational and phenotypic state of the tumor during the course of disease. However, the efficient detection of glioma CTCs has proven to be challenging due to the lack of consistently expressed tumor markers and high inter- and intra-tumor heterogeneity. Thus, for this field to progress, an omnipresent but specific marker of glioma CTCs is required. In this article, we demonstrate how the recombinant malaria VAR2CSA protein (rVAR2) can be used for the capture and detection of glioma cell lines that are spiked into blood through binding to a cancer-specific oncofetal chondroitin sulfate (ofCS). When using rVAR2 pull-down from glioma cells, we identified a panel of proteoglycans, known to be essential for glioma progression. Finally, the clinical feasibility of this work is supported by the rVAR2-based isolation and detection of CTCs from glioma patient blood samples, which highlights ofCS as a potential clinical target for CTC isolation. View Full-Text
Keywords: circulating tumor cells (CTCs); glioma; biomarker; rVAR2; malaria; enrichment and detection technologies circulating tumor cells (CTCs); glioma; biomarker; rVAR2; malaria; enrichment and detection technologies
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Bang-Christensen, S.R.; Pedersen, R.S.; Pereira, M.A.; Clausen, T.M.; Løppke, C.; Sand, N.T.; Ahrens, T.D.; Jørgensen, A.M.; Lim, Y.C.; Goksøyr, L.; Choudhary, S.; Gustavsson, T.; Dagil, R.; Daugaard, M.; Sander, A.F.; Torp, M.H.; Søgaard, M.; Theander, T.G.; Østrup, O.; Lassen, U.; Hamerlik, P.; Salanti, A.; Agerbæk, M.Ø. Capture and Detection of Circulating Glioma Cells Using the Recombinant VAR2CSA Malaria Protein. Cells 2019, 8, 998.

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