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 FormationReportar como inadecuado




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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 Kd 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.



Autor: Rassa Faryammanesh, Tobias Lange, Eileen Magbanua, Sina Haas, Cindy Meyer, Daniel Wicklein, Udo Schumacher, Ulrich Hahn

Fuente: http://plos.srce.hr/



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