The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

Mette Ø. Agerbæk, Sara R. Bang-Christensen, Ming-Hsin Yang, Thomas M. Clausen, Marina A. Pereira, Shreya Sharma, Sisse B. Ditlev, Morten A. Nielsen, Swati Choudhary, Tobias Gustavsson, Poul H. Sorensen, Tim Meyer, David Propper, Jonathan Shamash, Thor G. Theander, Alexandra Aicher, Mads Daugaard, Christopher Heeschen () and Ali Salanti ()
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Mette Ø. Agerbæk: Copenhagen University Hospital
Sara R. Bang-Christensen: Copenhagen University Hospital
Ming-Hsin Yang: Queen Mary University of London
Thomas M. Clausen: Copenhagen University Hospital
Marina A. Pereira: Copenhagen University Hospital
Shreya Sharma: Queen Mary University of London
Sisse B. Ditlev: Copenhagen University Hospital
Morten A. Nielsen: Copenhagen University Hospital
Swati Choudhary: Copenhagen University Hospital
Tobias Gustavsson: Copenhagen University Hospital
Poul H. Sorensen: British Columbia Cancer Research Centre
Tim Meyer: University College London
David Propper: Barts Health NHS
Jonathan Shamash: Barts Health NHS
Thor G. Theander: Copenhagen University Hospital
Alexandra Aicher: Queen Mary University of London
Mads Daugaard: Vancouver Prostate Centre
Christopher Heeschen: Queen Mary University of London
Ali Salanti: Copenhagen University Hospital

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial–mesenchymal transition of cancer cells. In 25 stage I–IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies.

Date: 2018
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DOI: 10.1038/s41467-018-05793-2

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