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Regulation of fibrin-mediated tumor cell adhesion to the endothelium using anti-thrombin aptamer

Erin R Gaddes1, Deborah Lee1, Gregory Gydush1

  • 1Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA.

Experimental Cell Research
|October 21, 2015
PubMed

Insights

An anti-thrombin aptamer inhibits soluble fibrin generation, reducing tumor cell adhesion and metastasis. This molecular intervention shows promise for cancer therapy by targeting key steps in the metastatic pathway.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Soluble fibrin (sFn) acts as a cross-linker, mediating tumor cell adhesion to endothelium.
  • sFn is generated by thrombin-mediated cleavage of fibrinogen (Fg), a process linked to vascular injury and tumor microenvironments.
  • Targeting thrombin's conversion of Fg to sFn presents a therapeutic strategy to inhibit cancer metastasis.

Purpose of the Study:

  • To investigate the efficacy of an anti-thrombin oligonucleotide aptamer in reducing tumor cell arrest.
  • To demonstrate the molecular and cellular mechanisms underlying the aptamer's inhibitory effects.

Main Methods:

  • Assessed aptamer binding to thrombin under dynamic flow conditions.
  • Examined aptamer's inhibition of thrombin-mediated Fg conversion to sFn.
  • Evaluated aptamer's effect on sFn-mediated tumor cell adhesion at various physiological shear rates.

Main Results:

  • The anti-thrombin aptamer successfully inhibited thrombin-mediated Fg conversion.
  • Aptamer treatment reduced sFn-mediated tumor cell adhesion in a concentration-dependent manner.
  • The aptamer demonstrated efficacy in reducing tumor cell adhesion under dynamic flow and physiological shear rates.

Conclusions:

  • Oligonucleotide aptamers targeting thrombin are effective in inhibiting tumor cell adhesion.
  • This aptamer-based approach shows significant potential as a therapeutic strategy to reduce cancer metastasis.
  • The findings highlight aptamers as promising regulators of tumor cell adhesion and metastatic activity.
Keywords:
AptamersCell–cell interactionsMolecular inhibitorMolecular recognitionTumor microenvironment

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