Related Experiment Video
Updated: Sep 26, 2026
Extracellular Vesicle Tissue Factor Activity Assay
Published on: December 29, 2023
Soluble tissue factor induces coagulation on tumor endothelial cells in vivo if coadministered with low-dose
Jana Philipp1, Ariane Dienst, Maike Unruh
1Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany.
Objective:
This study was performed to evaluate the mechanisms leading to tumor vessel occlusion by tissue factor-based drugs, which are used in vascular targeting approaches for the treatment of malignant tumors.
Methods And Results:
The effects of nontargeted soluble tissue factor were evaluated in vitro and in vivo. Tumor-bearing mice were treated with (1) the extracellular portion of tissue factor (soluble tissue factor), (2) low nontoxic doses of lipopolysaccharides, or (3) a combination thereof. The combination treatment showed the best effects and resulted in selective thrombosis of tumor vessels. On the basis of our data from subsequent in vitro analyses, including surface plasmon resonance measurements and endothelial cell based coagulation assays, we propose a model on how soluble tissue factor, although lacking its membrane anchor, can promote selective tumor vessel occlusion.
Conclusions:
To our knowledge, this is the first report to describe the molecular mechanisms of coagulation induction by untargeted soluble tissue factor in vivo. Combination treatments including soluble tissue factor might represent an alternative vascular targeting approach for the treatment of malignant tumors.
Insights
This study reveals how soluble tissue factor selectively causes tumor vessel occlusion. Combination therapy with soluble tissue factor and lipopolysaccharides offers a promising vascular targeting strategy for cancer treatment.
Area of Science:
- Biochemistry
- Oncology
- Vascular Biology
Background:
- Vascular targeting strategies aim to disrupt tumor blood supply.
- Tissue factor (TF) plays a crucial role in the coagulation cascade.
- Soluble TF (sTF) has been explored for therapeutic applications.
Purpose of the Study:
- To elucidate the mechanisms by which soluble tissue factor induces tumor vessel occlusion.
- To evaluate the efficacy of combination therapy using sTF for cancer treatment.
- To propose a model for sTF-mediated vascular targeting.
Main Methods:
- In vitro and in vivo experiments were conducted.
- Tumor-bearing mice were treated with sTF, lipopolysaccharides (LPS), or a combination.
- Surface plasmon resonance and endothelial cell-based coagulation assays were performed.
Main Results:
- Combination treatment of sTF and LPS demonstrated significant selective thrombosis of tumor vessels.
- sTF, despite lacking its membrane anchor, effectively promoted tumor vessel occlusion.
- Proposed a molecular model for sTF-driven coagulation and vascular targeting.
Conclusions:
- This study provides the first description of in vivo coagulation induction by untargeted soluble tissue factor.
- Combination therapies involving sTF represent a potential alternative vascular targeting approach for malignant tumors.
- Further research into sTF-based therapies could advance cancer treatment options.
