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
- Link:
- Autor/in:
- Erscheinungsjahr:
- 2014
- Medientyp:
- Text
- Schlagworte:
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- Aptamers, Nucleotide/pharmacology
- Cell Adhesion/drug effects
- Cell Proliferation/drug effects
- Cells, Cultured
- Colorectal Neoplasms/drug therapy
- E-Selectin/chemistry
- Endothelium, Vascular/drug effects
- Humans
- Leukemia/drug therapy
- Lung/blood supply
- P-Selectin/antagonists & inhibitors
- SELEX Aptamer Technique
- Transendothelial and Transepithelial Migration/drug effects
- Beschreibung:
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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 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.
- Lizenz:
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- info:eu-repo/semantics/openAccess
- Quellsystem:
- Forschungsinformationssystem der UHH
Interne Metadaten
- Quelldatensatz
- oai:www.edit.fis.uni-hamburg.de:publications/3c34a563-6951-4ddb-9c78-03e7e58214ce