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.
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.
Hamburg University, MIN-Faculty, Chemistry Department, Institute for Biochemistry and Molecular Biology, Hamburg, Germany.
Rassa
R
Faryammanesh
University Medical Center Hamburg-Eppendorf, University Cancer Center, Institute of Anatomy and Experimental Morphology, Hamburg, Germany.
Tobias
T
Lange
Hamburg University, MIN-Faculty, Chemistry Department, Institute for Biochemistry and Molecular Biology, Hamburg, Germany.
Eileen
E
Magbanua
Hamburg University, MIN-Faculty, Chemistry Department, Institute for Biochemistry and Molecular Biology, Hamburg, Germany.
Sina
S
Haas
Hamburg University, MIN-Faculty, Chemistry Department, Institute for Biochemistry and Molecular Biology, Hamburg, Germany.
Cindy
C
Meyer
University Medical Center Hamburg-Eppendorf, University Cancer Center, Institute of Anatomy and Experimental Morphology, Hamburg, Germany.
Daniel
D
Wicklein
University Medical Center Hamburg-Eppendorf, University Cancer Center, Institute of Anatomy and Experimental Morphology, Hamburg, Germany.
Udo
U
Schumacher
Hamburg University, MIN-Faculty, Chemistry Department, Institute for Biochemistry and Molecular Biology, Hamburg, Germany.
Ulrich
U
Hahn
D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D019040:E-Selectin / Q000737:chemistry* / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D019007:P-Selectin / Q000037:antagonists & inhibitors* / Q000235:genetics; D052156:SELEX Aptamer Technique; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*
D052157:Aptamers, Nucleotide; D019040:E-Selectin; D019007:P-Selectin