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

Nat Commun. 2018 Aug 16;9(1):3279. doi: 10.1038/s41467-018-05793-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Antigens, Protozoan / metabolism*
  • Cell Line, Tumor
  • Cell Separation
  • Epithelial Cell Adhesion Molecule / metabolism*
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Magnetics
  • Male
  • Mesoderm / metabolism
  • Microspheres
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Binding
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Recombinant Proteins / metabolism


  • Antigens, Protozoan
  • Epithelial Cell Adhesion Molecule
  • KRAS protein, human
  • Recombinant Proteins
  • VAR2CSA protein, Plasmodium falciparum
  • Proto-Oncogene Proteins p21(ras)