Focus on molecules: heparanase.

نویسندگان

  • Yinghui Zhang
  • Denise S Ryan
  • Kraig S Bower
  • Neta Ilan
  • Israel Vlodavsky
  • Gordon W Laurie
چکیده

Heparanase (NP_001092010) is a heparin-binding endo-bD-glucuronidase expressed by normal lacrimal gland (GEO Profiles: GDS1361), corneal epithelia (Berk et al., 2004), retinal pigment epithelium/choroid, lens (NEIBank) and some non-ocular tissues. Heparanase is over-expressed in essentially all human tumors examined. Western blotting suggests that heparanase is a constituent of normal tears (Ma, Laurie, unpublished). 119 37 pg/ml of active heparanase has been detected in normal saliva. Heparanase belongs to the glycoside hydrolase family 79. The heparanase gene ‘HPSE’ comprises fourteen exons over 39.8 kb of human chromosome 4, and forty-three orthologues have been documented (Ensembl release 57). HPSE is wellconserved from bony fish to human. Secreted heparanase in humans is 508 amino acids long, with a theoretical molecular weight and pI of 57.7 kDa and 9.2, respectively. Migration in SDS PAGE is approximately 65 kDa, in keeping with N-linked high mannose glycosylation at as many as six predicted sites (NetNGlyc 1.0). No O-glycosylation is predicted above threshold (NetOGlyc 3.1). Three splice variants have been recently reported (Barash et al., 2010) which vary in amino acid length, predicted molecular weight and charge as follows: 1) ‘T5’: 15.6 kDa and pI 6.9; 2)

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Impact of Heparanase and the Tumor Microenvironment on Cancer Metastasis and Angiogenesis: Basic Aspects and Clinical Applications

Heparanase is an endo-β-D-glucuronidase that cleaves heparan sulfate (HS) side chains at a limited number of sites, activity that is strongly implicated with cell invasion associated with cancer metastasis, a consequence of structural modification that loosens the extracellular matrix barrier. Heparanase activity is also implicated in neovascularization, inflammation, and autoimmunity, involvin...

متن کامل

Heparanase and heparanase 2 display differently deregulation in neuroendocrine tumors, depending on their differentiation grade.

Heparanase is a glucuronidase that appears upregulated in many human cancers and is involved in cellular invasion and tumor metastasis. Heparanase 2 is a homologue of heparanase that lacks enzymatic activity and displays anti-metastatic features. The aim of this work was to analyze the expression of both molecules in neuroendocrine tumors. We investigated the transcription of heparanases in lun...

متن کامل

Kinetic analysis and molecular modeling of the inhibition mechanism of roneparstat (SST0001) on human heparanase.

Heparanase is a β-d-glucuronidase which cleaves heparan sulfate chains in the extracellular matrix and on cellular membranes. A dysregulated heparanase activity is intimately associated with cell invasion, tumor metastasis and angiogenesis, making heparanase an attractive target for the development of anticancer therapies. SST0001 (roneparstat; Sigma-Tau Research Switzerland S.A.) is a non-anti...

متن کامل

P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins.

Vascular cell adhesion molecules, P- and L-selectins, facilitate metastasis of cancer cells in mice by mediating interactions with platelets, endothelium, and leukocytes. Heparanase is an endoglycosidase that degrades heparan sulfate of extracellular matrix, thereby promoting tumor invasion and metastasis. Heparin is known to efficiently attenuate metastasis in different tumor models. Here we i...

متن کامل

Molecular behavior adapts to context: heparanase functions as an extracellular matrix-degrading enzyme or as a T cell adhesion molecule, depending on the local pH

Migration of lymphocytes into inflammatory sites requires their adhesion to the vascular endothelium and subendothelial extracellular matrix (ECM). The ensuing penetration of the ECM is associated with the expression of ECM-degrading enzymes, such as endo-beta-D glucuronidase (heparanase), which cleaves heparan sulfate (HS) proteoglycans. We now report that, depending on the local pH, a mammali...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Experimental eye research

دوره 91 4  شماره 

صفحات  -

تاریخ انتشار 2010