Optimization of rVAR2-Based Isolation of Cancer Cells in Blood for Building a Robust Assay for Clinical Detection of Circulating Tumor Cells

Int J Mol Sci. 2020 Mar 31;21(7):2401. doi: 10.3390/ijms21072401.

Abstract

Early detection and monitoring of cancer progression is key to successful treatment. Therefore, much research is invested in developing technologies, enabling effective and valuable use of non-invasive liquid biopsies. This includes the detection and analysis of circulating tumor cells (CTCs) from blood samples. Recombinant malaria protein VAR2CSA (rVAR2) binds a unique chondroitin sulfate modification present on the vast majority of cancers and thereby holds promise as a near-universal tumor cell-targeting reagent to isolate CTCs from complex blood samples. This study describes a technical approach for optimizing the coupling of rVAR2 to magnetic beads and the development of a CTC isolation platform targeting a range of different cancer cell lines. We investigate both direct and indirect approaches for rVAR2-mediated bead retrieval of cancer cells and conclude that an indirect capture approach is most effective for rVAR2-based cancer cell retrieval.

Keywords: Circulating tumor cells (CTCs); cancer; diagnostics; enrichment technologies; rVAR2; rare cell isolation.

MeSH terms

  • Antigens, Protozoan / genetics*
  • Cell Line, Tumor
  • Chondroitin Sulfates / metabolism
  • Early Detection of Cancer / methods*
  • Humans
  • Magnetics
  • Neoplastic Cells, Circulating / pathology*
  • Recombinant Proteins

Substances

  • Antigens, Protozoan
  • Recombinant Proteins
  • VAR2CSA protein, Plasmodium falciparum
  • Chondroitin Sulfates