Shafat Itay, Barak Ayelet Ben, Postovsky Sergey, Elhasid Ronit, Ilan Neta, Vlodavsky Israel, Arush Miriam Weyl Ben
Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Neoplasia. 2007 Nov;9(11):909-16. doi: 10.1593/neo.07673.
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.
乙酰肝素酶是一种内切糖苷酶，可特异性切割硫酸乙酰肝素蛋白聚糖的硫酸乙酰肝素（HS）侧链，硫酸乙酰肝素蛋白聚糖是细胞外基质（ECM）和细胞表面的主要蛋白聚糖。越来越多的原发性人类肿瘤中都有乙酰肝素酶上调的记录，这与术后生存率降低和肿瘤血管生成增强相关。本研究的目的是使用酶联免疫吸附测定（ELISA）方法测定从儿科癌症患者采集的血样中的乙酰肝素酶水平。与健康对照组相比，癌症患者血浆中的乙酰肝素酶水平升高了四倍（分别为664±143与163±18 pg/ml）。评估抗癌治疗后的血浆样本发现乙酰肝素酶水平降低（664±143与429±82 pg/ml），差异具有高度统计学意义（P = 0.0048）。在重新分期时达到完全缓解（CR）或非常好的部分缓解（VGPR）的55例患者中，41例（74.5%）的乙酰肝素酶量较低，而14例患者（25.5%）的血浆乙酰肝素酶量相似或更高。所有9例病情稳定或进展的患者在重新分期时乙酰肝素酶水平相似或升高。结果表明，儿科癌症患者血浆中的乙酰肝素酶水平升高，且与治疗反应性密切相关，这表明乙酰肝素酶水平可用于诊断和监测患者对抗癌治疗的反应。
