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.

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.

• Authors: Rassa Faryammanesh, Tobias Lange, Eileen Magbanua, Sina Haas, Cindy Meyer, Daniel Wicklein, Udo Schumacher, Ulrich Hahn
• Journal: PloS one (PLoS One) Vol. 9 Issue 4 Pg. e93173 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24699049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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