Heparanase levels are elevated in the plasma of pediatric cancer patients and correlate with response to anticancer treatment

Itay Shafat, Ayelet Ben Barak, Sergey Postovsky, Ronit Elhasid, Neta Ilan, Israel Vlodavsky*, Miriam Weyl Ben Arush

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans, the major proteoglycan in the extracellular matrix (ECM) and cell surfaces. Heparanase upregulation was documented in an increasing number of primary human tumors, correlating with reduced postoperative survival rate and enhanced tumor angiogenesis. The purpose of the current study was to determine heparanase levels in blood samples collected from pediatric cancer patients using an ELISA method. Heparanase levels were elevated four-fold in the plasma of cancer patients compared with healthy controls (664 ± 143 vs 163 ± 18 pg/ml, respectively). Evaluating plasma samples following anticancer therapy revealed reduced heparanase levels (664 ± 143 vs 429 ± 82 pg/ml), differences that are statistically highly significant (P = .0048). Of the 55 patients with complete remission (CR) or very good partial remission (VGPR) at restaging, 41 (74.5%) had lower heparanase amounts, whereas 14 patients (25.5%) had similar or higher amounts of plasma heparanase. All nine patients with stable or advancing disease had similar or elevated levels of heparanase on restaging. The results show that heparanase levels are elevated in the plasma of pediatric cancer patients and closely correlate with treatment responsiveness, indicating that heparanase levels can be used to diagnose and monitor patient's response to anticancer treatment.

Original languageEnglish
Pages (from-to)909-916
Number of pages8
JournalNeoplasia
Volume9
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Funding

FundersFunder number
Deutsches Krebsforschungszentrum and Israel’s Ministry of Sciences and Technology
National Institutes of Health
National Cancer InstituteR01CA106456
Israel Cancer Research Fund
Israel Science Foundation549/06

    Keywords

    • Anticancer treatment
    • ELISA
    • Heparanase
    • Marker

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