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Heparanase coagulation and cancer progression
1Department of Haematology, Thrombosis and Haemostasis Unit, Rambam Medical Center, Haifa, Israel.
Best Practice & Research. Clinical Haematology
|March 17, 2009
Summary
Heparanase enzyme promotes cancer spread and blood clot formation by increasing tissue factor and affecting tissue factor pathway inhibitor. Heparin
Area of Science:
- Biochemistry
- Oncology
- Hematology
Background:
- Heparanase (HPSE) cleaves heparan sulphate (HS), impacting cancer metastasis and angiogenesis.
- HPSE overexpression correlates with increased tissue factor (TF) in various cancers.
- HPSE influences the regulation of tissue factor pathway inhibitor (TFPI).
Purpose of the Study:
- To investigate the role of heparanase in regulating tissue factor and tissue factor pathway inhibitor.
- To explore the mechanisms underlying heparanase-mediated induction of TF and TFPI.
- To assess the implications of heparanase's involvement in the coagulation pathway.
Main Methods:
- Assessing TF and TFPI levels in cancer cells and transgenic mice with heparanase overexpression.
- Utilizing recombinant heparanase to induce TF and TFPI in cell cultures.
- Investigating the role of p38 phosphorylation in TF induction.
- Demonstrating physical interaction between heparanase and TFPI.
Main Results:
- Heparanase overexpression and addition significantly increase TF levels and procoagulant activity.
- Heparanase induces TFPI expression and accumulation, partly through a physical interaction with TFPI.
- This interaction leads to TFPI dissociation from cell membranes, enhancing coagulation.
- Heparanase's role in TF/TFPI regulation is independent of its HS-cleaving activity.
Conclusions:
- Heparanase plays a significant role in the hemostatic system by modulating TF and TFPI.
- Heparanase's pro-metastatic and pro-angiogenic functions are linked to its procoagulant activity.
- Heparins, as heparanase inhibitors, may offer expanded therapeutic potential.
- Further research into heparanase's involvement in coagulation is warranted for cancer therapy.
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