TY - JOUR

T1 - Capture and Detection of Circulating Glioma Cells Using the Recombinant VAR2CSA Malaria Protein

AU - Bang-Christensen, Sara R

AU - Pedersen, Rasmus S

AU - Pereira, Marina A

AU - Clausen, Thomas M

AU - Løppke, Caroline

AU - Sand, Nicolai T

AU - Ahrens, Theresa D

AU - Jørgensen, Amalie M

AU - Lim, Yi Chieh

AU - Goksøyr, Louise

AU - Choudhary, Swati

AU - Gustavsson, Tobias

AU - Dagil, Robert

AU - Daugaard, Mads

AU - Sander, Adam F

AU - Torp, Mathias H

AU - Søgaard, Max

AU - Theander, Thor G

AU - Østrup, Olga

AU - Lassen, Ulrik

AU - Hamerlik, Petra

AU - Salanti, Ali

AU - Agerbæk, Mette Ø

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.3390/cells8090998

DO - 10.3390/cells8090998

M3 - Journal article

C2 - 31466397

VL - 8

JO - Cells

JF - Cells

SN - 2073-4409

IS - 9

M1 - 998

ER -