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Ralph D Sanderson, Michael Elkin, Alan C Rapraeger, Neta Ilan, Israel Vlodavsky
Because of its impact on multiple biological pathways, heparanase has emerged as a major regulator of cancer, inflammation and other disease processes. Heparanase accomplishes this by degrading heparan sulfate which regulates the abundance and location of heparin-binding growth factors thereby influencing multiple signaling pathways that control gene expression, syndecan shedding and cell behavior. In addition, heparanase can act via non-enzymatic mechanisms that directly activate signaling at the cell surface...
October 18, 2016: FEBS Journal
Li Jia, Shutao Ma
No abstract text is available yet for this article.
October 11, 2016: European Journal of Medicinal Chemistry
Olga Vornicova, Ilanit Boyango, Sari Feld, Inna Naroditsky, Olga Kazarin, Yaniv Zohar, Yariv Tiram, Neta Ilan, Ofer Ben-Izhak, Israel Vlodavsky, Gil Bar-Sela
BACKGROUND: Heparanase expression is induced in many types of cancers, including melanoma, and promotes tumor growth, angiogenesis and metastasis. However, there is insufficient data regarding heparanase expression in the metastatic lesions that are the prime target for anti-cancer therapeutics. To that end, we examined heparanase expression in metastatic melanoma and its correlation with clinical parameters. RESULTS: Heparanase staining was detected in 88% of the samples, and was strong in 46%...
October 6, 2016: Oncotarget
Michela Asperti, Tanja Stuemler, Maura Poli, Magdalena Gryzik, Lena Lifshitz, Esther G Meyron-Holtz, Israel Vlodavsky, Paolo Arosio
Hepcidin is the key regulator of systemic iron availability that acts by controlling the degradation of the iron exporter ferroportin. It is expressed mainly in the liver and regulated by iron, inflammation, erythropoiesis and hypoxia. The various agents that control its expression act mainly via the BMP6/SMAD signaling pathway. Among them are exogenous heparins, which are strong hepcidin repressors with a mechanism of action not fully understood but that may involve the competition with the structurally similar endogenous Heparan Sulfates (HS)...
2016: PloS One
Liduan Zheng, Wanju Jiao, Huajie Song, Hongxia Qu, Dan Li, Hong Mei, Yajun Chen, Feng Yang, Huanhuan Li, Kai Huang, Qiangsong Tong
Previous studies have indicated that as the only mammalian endo-β-D-glucuronidase, heparanase (HPSE) is up-regulated and associated with poor prognosis in gastric cancer, while the underlying mechanisms still remain to be determined. Herein, through integrative analysis of public datasets, we found microRNA-558 (miR-558) and SMAD family member 4 (Smad4) as the crucial transcription regulators of HPSE expression in gastric cancer, with their adjacent target sites within the promoter of HPSE. We identified that endogenous miR-558 activated the transcription and expression of HPSE in gastric cancer cell lines...
2016: Cell Death & Disease
Giuliana Cassinelli, Nadia Zaffaroni, Cinzia Lanzi
Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression...
September 22, 2016: Cancer Letters
Shirin Mahmoodi, Navid Nezafat, Abolfazl Barzegar, Monica Negahdaripour, Ali-Reza Nikanfar, Nosratollah Zarghami, Younes Ghasemi
Breast cancer (BC) remains as one of the important causes of cancer deaths among women globally. Therefore, finding an effective treatment for BC is really needed. Cancer immunotherapy, as an emerging field, has a notable role in BC therapy. Peptide vaccines possess an outstanding role among different strategies in cancer immunotherapy. In vaccine design for cancer, induction of cellular and humoral immune responses should be considered. In the current study, cytolytic T lymphocytes (CTL) epitopes were evoked from human epidermal growth factor receptor (HER2), mucin 1 protein (MUC1), and heparanase antigenic proteins; and helper T lymphocytes (HTL) epitopes were determined from survivin protein by various immunoinformatics servers...
September 14, 2016: Current Pharmaceutical Biotechnology
Hongxia Qu, Liduan Zheng, Wanju Jiao, Hong Mei, Dan Li, Huajie Song, Erhu Fang, Xiaojing Wang, Shiwang Li, Kai Huang, Qiangsong Tong
Heparanase (HPSE) is the only endo-β-D-glucuronidase that is correlated with the progression of neuroblastoma (NB), the most common extracranial malignancy in childhood. However, the mechanisms underlying HPSE expression in NB still remain largely unknown. Herein, through analyzing cis-regulatory elements and mining public microarray datasets, we identified SMAD family member 4 (Smad4) as a crucial transcription regulator of HPSE in NB. We demonstrated that Smad4 repressed the HPSE expression at the transcriptional levels in NB cells...
2016: Scientific Reports
Tiantian Ye, Hefeng Zhang, Ge Chen, Lei Shang, Shujun Wang
Tumor metastatic lymph node mapping has been widely used to predict the metastatic spread of primary tumor and guide the lymph node dissection in clinical practice. In this research, a new near-infrared (NIR)-emitting low molecular weight heparin (LMWHEP)-modified Cy7-loaded nanoliposome (LMWHEP-NLips/Cy7) was developed and had the particle size of about 80 nm and the fluorescence intensity of about 2300, which is optimal for metastatic lymph node uptake and imaging. The NIR-emitting nanoliposomes were designed by LMWHEP coating on the surface of Cy7-loaded nanoliposome (NLips/Cy7) according to electrostatic attraction...
September 1, 2016: Contrast Media & Molecular Imaging
Benjamin Heyman, Yiping Yang
Heparanase is an endo-β-D-glucuronidase capable of cleaving heparan sulfate (HS) side chains contributing to break down of the extracellular matrix. Increased expression of heparanase has been found in numerous malignancies, and is associated with a poor prognosis. It has generated significant interest as a potential anti-neoplastic target because of the multiple roles it plays in tumor growth and metastasis. The pro-tumorigenic effects of heparanase are enhanced by the release of HS side chains, with subsequent increase in bioactive fragments and increased cytokine levels; both promoting tumor invasion, angiogenesis and metastasis...
August 26, 2016: Experimental Hematology
Marjolein Garsen, Angelique L W M M Rops, Henry Dijkman, Brigith Willemsen, Toin H van Kuppevelt, Frans G Russel, Ton J Rabelink, Jo H M Berden, Thomas Reinheckel, Johan van der Vlag
Proteinuria is one of the first clinical signs of diabetic nephropathy and an independent predictor for the progression to renal failure. Cathepsin L, a lysosomal cysteine protease, can be involved in the development of proteinuria by degradation of proteins that are important for normal podocyte architecture, such as the CD2-associated protein, synaptopodin, and dynamin. Cathepsin L also activates heparanase, a heparan sulfate endoglycosidase previously shown to be crucial for the development of diabetic nephropathy...
November 2016: Kidney International
Soumi Kundu, Anqi Xiong, Argyris Spyrou, Grzegorz Wicher, Voichita D Marinescu, Per-Henrik D Edqvist, Lei Zhang, Magnus Essand, Anna Dimberg, Anja Smits, Neta Ilan, Israel Vlodavsky, Jin-Ping Li, Karin Forsberg-Nilsson
: Malignant glioma continues to be fatal, despite improved insight into its underlying molecular mechanisms. The most malignant form, glioblastoma (GBM), is characterized by aberrant activation of receptor tyrosine kinases (RTK) and infiltrative growth. Heparan sulfate proteoglycans (HSPGs), integral components of the extracellular matrix of brain tumors (HPSE), which cleaves HSPGs, for its role in glioma. This hypothesis was evaluated using tissue microarrays, GBM cells derived from patients, murine in vitro and in vivo can regulate activation of many RTK pathways...
August 26, 2016: Molecular Cancer Research: MCR
Satoshi Amano
Sun-exposed skin is characterized by superficial changes such as wrinkles, sagging and pigmentary changes, and also many internal changes in the structure and function of epidermis, basement membrane (BM) and dermis. These changes (so-called photoageing) are predominantly induced by the ultraviolet (UV) component of sunlight. Epidermis of UV-irradiated skin produced several enzymes such as matrix metalloproteinases (MMPs), urinary plasminogen activator (uPA)/plasmin and heparanase, which degrade dermal collagen fibres and elastic fibres in the dermis, and components of epidermal BM...
August 2016: Experimental Dermatology
Yonatan Crispel, Elena Axelman, Mifleh Tatour, Inna Kogan, Neta Nevo, Benjamin Brenner, Yona Nadir
Heparanase is implicated in angiogenesis and tumour progression. We previously demonstrated that heparanase might also affect the haemostatic system in a non-enzymatic manner. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (TF). Peptides that we generated from TF pathway inhibitor (TFPI)-2, which inhibit heparanase procoagulant activity, were recently demonstrated to attenuate inflammation in a sepsis mouse model. The present study was designated to explore peptides effects on tumour growth and vascularisation...
September 27, 2016: Thrombosis and Haemostasis
Marjolein Garsen, Angelique L Rops, Jinhua Li, Katrien van Beneden, Christiane van den Branden, Jo Hm Berden, Ton J Rabelink, Johan van der Vlag
Endothelial nitric oxide synthase (eNOS) deficiency exacerbates proteinuria and renal injury in several glomerular diseases, but the underlying mechanism is not fully understood. We recently showed that heparanase is essential for the development of experimental diabetic nephropathy and glomerulonephritis, and hypothesize that heparanase expression is regulated by eNOS. Here, we demonstrate that induction of adriamycin nephropathy (AN) in C57BL/6 eNOS-deficient mice leads to an increased glomerular heparanase expression accompanied with overt proteinuria, which was not observed in the AN-resistant wild type counterpart...
2016: PloS One
Lipeng Wang, Xiao Huang, Guiqing Kong, Haixiao Xu, Jiankui Li, Dong Hao, Tao Wang, Shasha Han, Chunlei Han, Yeying Sun, Xiangyong Liu, Xiaozhi Wang
Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure characterized by major pathologic mechanisms of increased microvascular permeability and inflammation. The glycocalyx lines on the endothelial surface, which determines the vascular permeability, and heparanase play pivotal roles in the degradation of heparan sulfate (HS). HS is the major component of the glycocalyx. The aim of this study is to examine the effects of Ulinastatin (UTI) on vascular permeability and pulmonary endothelial glycocalyx dysfunction induced by lipopolysaccharide (LPS)...
September 16, 2016: Biochemical and Biophysical Research Communications
Valentina Masola, Gianluigi Zaza, Giovanni Gambaro, Maurizio Onisto, Gloria Bellin, Gisella Vischini, Iyad Khamaysi, Ahmad Hassan, Shadi Hamoud, Omri Nativ, Samuel N Heyman, Antonio Lupo, Israel Vlodavsky, Zaid Abassi
BACKGROUND: Ischemia/reperfusion (I/R) is an important cause of acute renal failure and delayed graft function, and it may induce chronic renal damage by activating epithelial to mesenchymal transition (EMT) of renal tubular cells. Heparanase (HPSE), an endoglycosidase that regulates FGF-2 and TGFβ-induced EMT, may have an important role. Therefore, aim of this study was to evaluate its role in the I/R-induced renal pro-fibrotic machinery by employing in vitro and in vivo models. METHODS: Wild type (WT) and HPSE-silenced renal tubular cells were subjected to hypoxia and reoxygenation in the presence or absence of SST0001, an inhibitor of HPSE...
2016: PloS One
Souad Djaafar, Isabelle Dunand-Sautier, Carmen Gonelle-Gispert, Stephanie Lacotte, Ariane DE Agostini, Majno Petro, Laura Rubbia-Brandt, Philippe Morel, Christian Toso, Gilles Mentha
BACKGROUND/AIM: Low-molecular-weight heparin (LMWH) has been suggested to reduce the risk of cancer progression in both preclinical and clinical studies but the underlying mechanisms remain poorly explored. The aim of the study was to investigate the anti-metastatic role of enoxaparin, a clinically-used LMWH, in a murine model of colon cancer and to explore its underlying mechanisms. MATERIALS AND METHODS: Using a reproducible mouse model of colon carcinomas, we assessed the capacity of enoxaparin, a LMWH, to affect tumor metastasis of colon carcinoma cell lines in mice...
August 2016: Anticancer Research
Shuji Mikami, Mototsugu Oya, Ryuichi Mizuno, Takeo Kosaka, Masaru Ishida, Naoto Kuroda, Yoji Nagashima, Ken-Ichi Katsube, Yasunori Okada
The purpose of this article is to review the recent advances in renal cell carcinoma (RCC) from a pathological point of view. Because the genetic features and morphological characteristics have become major criteria for the classification of RCC, special techniques, such as immunohistochemistry, are essential to the differential diagnosis of renal tumors. Metastasis is frequently observed among the RCC patients with curative nephrectomy, and extracellular matrix-degrading enzymes, such as matrix metalloproteinases (MMP) and heparanase, play a key role in invasion and metastasis of RCC...
September 2016: Pathology International
Ahamed Hossain, Lamiya Tauhid, Ian Davenport, Thomas Huckaba, Richard Graves, Tarun Mandal, Syed Muniruzzaman, Syed A Ahmed, Partha S Bhattacharjee
PURPOSE: The cell surface LDL (low-density lipoprotein) receptor-related protein-1 (LRP-1) is important for lipid transport and several cell signaling processes. Human apolipoprotein E (apoE) is a ligand of LRP-1. We previously reported that a short peptide (apoEdp) mimicking the LRP-1 binding region of apoE prevents hyperglycemia-induced retinal endothelial cell dysfunction in vitro. The in-vivo outcome of apoE-based peptidomimetic inhibition of LRP-1 in the treatment of diabetic retinopathy is unknown...
July 21, 2016: Current Eye Research
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