Open AccessPre‐clinical and clinical significance of heparanase in Ewing’s sarcoma
Author(s) -
Shafat Itay,
BenArush Myriam Weyl,
Issakov Josephine,
Meller Isaac,
Naroditsky Inna,
Tortoreto Monica,
Cassinelli Giuliana,
Lanzi Cinzia,
Pisano Claudio,
Ilan Neta,
Vlodavsky Israel,
Zunino Franco
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01190.x
Subject(s) - heparanase , angiogenesis , metastasis , sarcoma , cancer research , immunostaining , heparan sulfate , immunohistochemistry , medicine , pathology , cancer , in vivo , heparin , biology , microbiology and biotechnology
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.