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.