SDA, a DNA aptamer inhibiting E- and P-selectin mediated adhesion of cancer and leukemia cells, the first and pivotal step in transendothelial migration during metastasis formation

PLoS One. 2014 Apr 3;9(4):e93173. doi: 10.1371/journal.pone.0093173. eCollection 2014.

Abstract

Endothelial (E-) and platelet (P-) selectin mediated adhesion of tumor cells to vascular endothelium is a pivotal step of hematogenous metastasis formation. Recent studies have demonstrated that selectin deficiency significantly reduces metastasis formation in vivo. We selected an E- and P-Selectin specific DNA Aptamer (SDA) via SELEX (Systematic Evolution of Ligands by EXponential enrichment) with a K(d) value of approximately 100 nM and the capability of inhibiting the interaction between selectin and its ligands. Employing human colorectal cancer (HT29) and leukemia (EOL-1) cell lines we could demonstrate an anti-adhesive effect for SDA in vitro. Under physiological shear stress conditions in a laminar flow adhesion assay, SDA inhibited dynamic tumor cell adhesion to immobilized E- or P-selectin. The stability of SDA for more than two hours allowed its application in cell-cell adhesion assays in cell culture medium. When adhesion of HT29 cells to TNFα-stimulated E-selectin presenting human pulmonary microvascular endothelial cells was analyzed, inhibition via SDA could be demonstrated as well. In conclusion, SDA is a potential new therapeutic agent that antagonizes selectin-mediated adhesion during metastasis formation in human malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • E-Selectin / chemistry*
  • E-Selectin / genetics
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Humans
  • Leukemia / drug therapy
  • Leukemia / genetics
  • Leukemia / pathology*
  • Lung / blood supply
  • Lung / cytology
  • Lung / metabolism
  • P-Selectin / antagonists & inhibitors*
  • P-Selectin / genetics
  • SELEX Aptamer Technique
  • Transendothelial and Transepithelial Migration / drug effects*

Substances

  • Aptamers, Nucleotide
  • E-Selectin
  • P-Selectin

Grants and funding

Forschungs- und Wissenschaftsstiftung Hamburg in the Forschungsverbund “Cell surface targeting”. Grant of the FAZIT-STIFTUNG to R.F. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.