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Heparanase multiple effects in cancer.

Yona Nadir1, Benjamin Brenner1

  • 1Thrombosis and Hemostasis Unit, Department of Hematology, Rambam Health Care Campus, Haifa, Israel.

Thrombosis Research
|May 28, 2014
PubMed
Summary
This summary is machine-generated.

Heparanase, an enzyme implicated in cancer metastasis, also promotes blood clotting through non-enzymatic functions. Targeting heparanase offers a potential therapeutic strategy for malignancies.

Keywords:
CancerEnzymaticHeparanaseNon-enzymaticProcoagulant

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Area of Science:

  • Biochemistry
  • Oncology
  • Hematology

Background:

  • Heparanase cleaves heparan sulfate, impacting tumor metastasis and angiogenesis.
  • Heparanase exhibits enzymatic and non-enzymatic functions, including growth factor regulation and cell signaling.
  • Previous studies indicated heparanase affects the hemostatic system non-enzymatically.

Purpose of the Study:

  • To investigate the non-enzymatic effects of heparanase on the hemostatic system.
  • To elucidate the mechanisms by which heparanase influences blood coagulation.
  • To evaluate heparanase as a potential therapeutic target in cancer.

Main Methods:

  • Assessed heparanase's impact on tissue factor (TF) expression and activity.
  • Investigated heparanase interaction with tissue factor pathway inhibitor (TFPI).
  • Measured factor Xa production and coagulation system activation.

Main Results:

  • Heparanase up-regulated TF expression and enhanced TF activity.
  • Heparanase caused TFPI dissociation from cell surfaces, increasing coagulation.
  • Heparanase directly boosted TF activity, leading to increased factor Xa generation.

Conclusions:

  • Heparanase possesses pro-coagulant functions mediated by TF and TFPI.
  • Heparanase's prometastatic, pro-angiogenic, and pro-coagulant roles suggest therapeutic potential.
  • Targeting heparanase may offer a novel strategy for treating human malignancies.