期刊
EXPERIMENTAL CELL RESEARCH
卷 339, 期 2, 页码 417-426出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2015.10.010
关键词
Tumor microenvironment; Molecular inhibitor; Aptamers; Cell-cell interactions; Molecular recognition
资金
- U.S. National Science Foundation [1322332, 1330663]
- Penn State College of Engineering Research Initiative program
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1322332] Funding Source: National Science Foundation
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1330663] Funding Source: National Science Foundation
Molecular intervention during transient stages of various metastatic pathways may lead to development of promising therapeutic technologies. One of such involves soluble fibrin (sFn) that has been implicated as a cross-linker between circulating blood or tumor cells and endothelial cell receptors, promoting cell arrest on the endothelium during circulation. sFn generation is a result of thrombin-mediated fibrinogen (Fg) cleavage due to either vascular injuries or a tumor microenvironment. For cancer therapy, thrombin-mediated conversions of Fg to sFn thus serve as potential intervention points to decrease circulating tumor cell adhesion to the endothelium and subsequent metastatic events. The purpose of this work was to investigate the function of an anti-thrombin oligonucleotide aptamer in reducing tumor cell arrest. Both molecular and cellular interactions were examined to demonstrate the binding and inhibitory effects of anti-thrombin aptamer. The results show that the aptamer is capable of inhibiting thrombin-mediated Fg conversion, thereby reducing sFn-mediated tumor cell adhesion in a concentration-dependent manner. Notably, the aptamer is able to bind thrombin under dynamic flow conditions and reduce tumor cell adhesive events at various physiological shear rates. This study further indicates that oligonucleotide aptamers hold great promise as therapeutic regulators of tumor cell adhesion, and consequently, metastatic activity. (C) 2015 Elsevier Inc. All rights reserved.
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