Pre-clinical and Clinical Significance of Heparanase in Ewing's Sarcoma

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2010 Oct 30

PMID 21029368

Citations 32

Authors

Itay Shafat

Myriam Weyl Ben-Arush

Josephine Issakov

Isaac Meller

Inna Naroditsky

Monica Tortoreto

Giuliana Cassinelli

Cinzia Lanzi

Claudio Pisano

Neta Ilan

Israel Vlodavsky

Franco Zunino

Affiliations

Soon will be listed here.

Abstract

Heparanase is an endoglycosidase that specifically cleaves heparan sulphate side chains of heparan sulphate proteoglycans, activity that is strongly implicated in cell migration and invasion associated with tumour metastasis, angiogenesis and inflammation. Heparanase up-regulation was documented in an increasing number of human carcinomas, correlating with reduced post-operative survival rate and enhanced tumour angiogenesis. Expression and significance of heparanase in human sarcomas has not been so far reported. Here, we applied the Ewing's sarcoma cell line TC71 and demonstrated a potent inhibition of cell invasion in vitro and tumour xenograft growth in vivo upon treatment with a specific inhibitor of heparanase enzymatic activity (compound SST0001, non-anticoagulant N-acetylated, glycol split heparin). Next, we examined heparanase expression and cellular localization by immunostaining of a cohort of 69 patients diagnosed with Ewing's sarcoma. Heparanase staining was noted in all patients. Notably, heparanase staining intensity correlated with increased tumour size (P = 0.04) and with patients' age (P = 0.03), two prognostic factors associated with a worse outcome. Our study indicates that heparanase expression is induced in Ewing's sarcoma and associates with poor prognosis. Moreover, it encourages the inclusion of heparanase inhibitors (i.e. SST0001) in newly developed therapeutic modalities directed against Ewing's sarcoma and likely other malignancies.

Citing Articles

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Dysregulated heparan sulfate proteoglycan metabolism promotes Ewing sarcoma tumor growth.

Vasileva E, Warren M, Triche T, Amatruda J Elife. 2022; 11.

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Ultrasensitive small molecule fluorogenic probe for human heparanase.

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Non-Anticoagulant Heparins as Heparanase Inhibitors.

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