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Related Experiment Video

Updated: Jul 3, 2026

Extracellular Vesicle Tissue Factor Activity Assay
03:53

Extracellular Vesicle Tissue Factor Activity Assay

Published on: December 29, 2023

Heparanase, tissue factor, and cancer.

Yona Nadir1, Israel Vlodavsky, Benjamin Brenner

  • 1Thrombosis and Hemostasis Unit, Department of Hematology, Rambam Medical Center, Haifa, Israel. ynadir@netvision.net.il

Seminars in Thrombosis and Hemostasis
|July 23, 2008
PubMed
Summary

Heparanase enzyme promotes cancer spread and blood clots by increasing tissue factor (TF) and tissue factor pathway inhibitor (TFPI). Heparin

Area of Science:

  • Biochemistry
  • Oncology
  • Hematology

Background:

  • Heparanase is an enzyme that degrades heparan sulfate.
  • Heparanase activity is linked to cancer metastasis and angiogenesis.
  • Heparanase influences coagulation factors.

Purpose of the Study:

  • To investigate the role of heparanase in regulating tissue factor (TF) and tissue factor pathway inhibitor (TFPI).
  • To explore the mechanisms by which heparanase affects TF and TFPI levels.
  • To assess the implications for heparanase-targeted therapies.

Main Methods:

  • Overexpression of heparanase in cancer cell lines and transgenic mice.
  • Treatment of cells with recombinant heparanase.
  • Measurement of TF and TFPI levels and activity.

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  • Analysis of p38 phosphorylation.
  • Demonstration of physical interaction between heparanase and TFPI.
  • Main Results:

    • Heparanase overexpression or addition increased TF levels and procoagulant activity.
    • Heparanase induced TF via p38 phosphorylation.
    • Heparanase overexpression or addition increased TFPI expression and accumulation.
    • A physical interaction between heparanase and TFPI was observed, leading to TFPI dissociation from cell membranes.
    • Heparanase's effect on TFPI appeared independent of its enzymatic activity.

    Conclusions:

    • Heparanase plays a significant role in regulating the TF/TFPI pathway.
    • Heparanase promotes a prothrombotic state, contributing to cancer progression.
    • Heparins, as heparanase inhibitors, may have expanded therapeutic potential beyond anticoagulation.