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Amit Katz, Uri Barash, Ilanit Boyango, Sari Feld, Yaniv Zohar, Edward Hammond, Neta Ilan, Ran Kremer, Israel Vlodavsky
Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. HS mimicking compounds that inhibit heparanase enzymatic activity were examined in numerous preclinical cancer models. While these studies utilized established tumor cell lines, the current study utilized, for the first time, patient-derived xenografts (PDX) which better resemble the behavior and drug responsiveness of a given cancer patient...
April 10, 2018: Oncotarget
Andreas Margraf, Jan M Herter, Katharina Kühne, Anika Stadtmann, Thomas Ermert, Manuel Wenk, Melanie Meersch, Hugo Van Aken, Alexander Zarbock, Jan Rossaint
BACKGROUND: Increased vascular permeability is a pathophysiological hallmark of sepsis and results in increased transcapillary leakage of plasma fluid, hypovolemia, and interstitial edema formation. 6% hydroxyethyl starch (HES 130/0.4) is commonly used to treat hypovolemia to maintain adequate organ perfusion and oxygen delivery. The present study was designed to investigate the effects of 6% HES 130/0.4 on glycocalyx integrity and vascular permeability in lipopolysaccharide (LPS)-induced pulmonary inflammation and systemic inflammation in mice...
May 1, 2018: Critical Care: the Official Journal of the Critical Care Forum
Yona Nadir, Benjamin Brenner
Activated proteins of the coagulation system are known to enhance angiogenesis and tumor growth. Notably, the main coagulation proteins involved are those of the extrinsic and common pathways. Strategies to attenuate tumor progression by decreasing activation of the coagulation system may be compromised by an increased risk of bleeding. Currently, studies using derivatives of heparins devoid of or with low anticoagulant activity are being conducted. Heparanase protein was demonstrated to enhance tissue factor activity...
April 2018: Thrombosis Research
Hong-Ru Chen, Chiao-Hsuan Chao, Ching-Chuan Liu, Tzong-Shiann Ho, Huey-Pin Tsai, Guey-Chuen Perng, Yee-Shin Lin, Jen-Ren Wang, Trai-Ming Yeh
Vascular leakage is one of the salient characteristics of severe dengue. Nonstructural protein 1 (NS1) of dengue virus (DENV) can stimulate endothelial cells to secrete endothelial hyperpermeability factor, macrophage migration inhibitory factor (MIF), and the glycocalyx degradation factor heparanase 1 (HPA-1). However, it is unclear whether MIF is directly involved in NS1-induced glycocalyx degradation. In this study, we observed that among NS1, MIF and glycocalyx degradation-related molecules, the HPA-1, metalloproteinase 9 (MMP-9) and syndecan 1 (CD138) serum levels were all increased in dengue patients, and only NS1 and MIF showed a positive correlation with the CD138 level in severe patients...
April 27, 2018: PLoS Pathogens
Monica Galli, Manik Chatterjee, Mariella Grasso, Giorgina Specchia, Hila Magen, Hermann Einsele, Ivana Celeghini, Paola Barbieri, David Paoletti, Silvia Pace, Ralph D Sanderson, Alessandro Rambaldi, Arnon Nagler
No abstract text is available yet for this article.
April 26, 2018: Haematologica
Ning Li, Meng-Meng Jie, Min Yang, Li Tang, Si-Yuan Chen, Xue-Mei Sun, Bo Tang, Shi-Ming Yang
Heparanase (HPA) is ubiquitously expressed in various metastatic malignant tumors; previous studies have demonstrated that HPA was a potential tumor-associated antigen (TAA) for tumor immunotherapy. We sought to evaluate the feasibility of HPA as a common TAA for magnetic resonance imaging (MRI) of tumor metastasis and its potential application in tumor molecular imaging. We prepared a targeted probe based on magnetic gold nanoparticles coupled with an anti-HPA antibody for the specific detection of HPA by MRI...
April 18, 2018: Nanoscale Research Letters
Elisabeth Zechendorf, Phillip Vaßen, Jieyi Zhang, Ahmed Hallawa, Antons Martincuks, Oliver Krenkel, Gerhard Müller-Newen, Tobias Schuerholz, Tim-Philipp Simon, Gernot Marx, Gerd Ascheid, Anke Schmeink, Guido Dartmann, Christoph Thiemermann, Lukas Martin
Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes...
2018: Frontiers in Immunology
Hao Jin, Min Cui
This study investigated the effect of transcriptional gene silencing of the heparanase gene on standard gallbladder carcinoma cells (GBC-SD). The miRNAs targeting the promoter region and coding region of the heparanase gene were designed and synthesized. We transfected four recombinant miRNA vectors into GBC-SD. We performed the wound healing assays and invasion assays. The result shows that the heparanase expression was significantly decreased by recombinant vectors in transfected GBC-SD cells (p < 0...
March 29, 2018: Bioscience, Biotechnology, and Biochemistry
Michael J Whitehead, Rhona McGonigal, Hugh J Willison, Susan C Barnett
Axon degeneration underlies many nervous system diseases; therefore understanding the regulatory signalling pathways is fundamental to identifying potential therapeutics. Previously, we demonstrated heparan sulphates (HS) as a potentially new target for promoting CNS repair. HS modulate cell signalling by both acting as cofactors in the formation of ligand-receptor complexes and in sequestering ligands in the extracellular matrix. The enzyme heparanase (Hpse) negatively regulates these processes by cleaving HS and releasing the attached proteins, thereby attenuating their ligand-receptor interaction...
March 26, 2018: Scientific Reports
Uri Barash, Moshe Lapidot, Yaniv Zohar, Cynthia Loomis, Andre Moreira, Sari Feld, Chandra Goparaju, Haining Yang, Edward Hammond, Ganlin Zhang, Jin-Ping Li, Neta Ilan, Arnon Nagler, Harvey I Pass, Israel Vlodavsky
Background: Mammalian cells express a single functional heparanase, an endoglycosidase that cleaves heparan sulfate and thereby promotes tumor metastasis, angiogenesis, and inflammation. Malignant mesothelioma is highly aggressive and has a poor prognosis because of the lack of markers for early diagnosis and resistance to conventional therapies. The purpose of this study was to elucidate the mode of action and biological significance of heparanase in mesothelioma and test the efficacy of heparanase inhibitors in the treatment of this malignancy...
March 21, 2018: Journal of the National Cancer Institute
(no author information available yet)
No abstract text is available yet for this article.
April 2018: Molecular Cancer Research: MCR
Wanju Jiao, Yajun Chen, Huajie Song, Dan Li, Hong Mei, Feng Yang, Erhu Fang, Xiaojing Wang, Kai Huang, Liduan Zheng, Qiangsong Tong
Recent studies reveal the emerging functions of enhancer RNAs (eRNAs) in gene expression. However, the roles of eRNAs in regulating the expression of heparanase (HPSE), an established endo-β-D-glucuronidase essential for cancer invasion and metastasis, still remain elusive. Herein, through comprehensive analysis of publically available FANTOM5 expression atlas and chromatin interaction dataset, we identified a super enhancer and its derived eRNA facilitating the HPSE expression (HPSE eRNA) in cancers. Gain-of-function and loss-of-function experiments indicated that HPSE eRNA facilitated the in vitro and in vivo tumorigenesis and aggressiveness of cancer cells...
May 2018: Oncogene
Ying-Xia Tan, Hao Cui, Lu-Ming Wan, Feng Gong, Xiao Zhang, Israel Vlodavsky, Jin-Ping Li
Heparanase, an endo-glucuronidase that specifically cleaves heparan sulfate, is upregulated in several pathological conditions. In this study, we aimed to find a correlation of heparanase expression and platelets production. In the transgenic mice overexpressing human heparanase (Hpa-tg), hematological analysis of blood samples revealed a significantly higher number of platelets in comparison with wild-type (Ctr) mice, while no significant difference was found in leukocytes and red blood cell number between the two groups...
February 19, 2018: Glycobiology
Olga Vornicova, Inna Naroditsky, Ilanit Boyango, Shlomit S Shachar, Tanya Mashiach, Neta Ilan, Israel Vlodavsky, Gil Bar-Sela
High levels of heparanase are detected in many types of tumors, associated with bad prognosis. Typically, heparanase levels are evaluated in a biopsy taken from the primary lesion, whereas its expression by the resulting metastases is most often unresolved. This becomes critically important as anti-heparanase compounds enter advanced clinical trials. Here, we examined the expression of heparanase in pairs of primary and the resulting distant metastases of breast carcinoma. Interestingly, we found that heparanase expression in the metastatic lesion does not always reflect its expression in the primary tumor...
January 19, 2018: Oncotarget
Elisa X Y Lim, Aroon Supramaniam, Hayman Lui, Peta Coles, Wai Suet Lee, Xiang Liu, Penny A Rudd, Lara J Herrero
Arthritogenic alphavirus infections often result in debilitating musculoskeletal disorders that affect the joints, muscle, and bone. In order to evaluate the infection profile of primary human skeletal muscle and chondrocyte cells to Ross River virus (RRV) in vitro, cells were infected at a multiplicity of infection (MOI) of 1 over a period of two days. Viral titers were determined by plaque assay and cytokine expression by Bio-Plex® assays using the supernatants harvested. Gene expression studies were conducted using total RNA isolated from cells...
February 15, 2018: Viruses
Nan Sheng, Lin Zhang, Shaofeng Yang
The present study aimed to measure the expression of microRNA (miRNA/miR) -429 in gastric cancer and investigate the associated mechanism of action. A total of 30 patients with gastric cancer who received radical or palliative resection at Jining No. 1 People's Hospital between January-October 2016 were included in the present study. Resected gastric cancer and tumor-adjacent tissues were resected. Gastric cancer BGC-823 cells were transfected with miR-429 mimics to induce the overexpression of miR-429, or transfected with small interfering (si)RNA of heparanase (HPSE) for the silencing of HPSE...
February 2018: Experimental and Therapeutic Medicine
Shuo Yang, Yong Liao, Qi Zhao, Yuqin Xie, Ai Zheng, Huajing Wan
The mitotic spindle, assembled by microtubule organization center (MTOC), is a critical structure required for proper chromosome segregation during mitosis. Studies demonstrated that defects of mitotic spindle assembling would result in chromosome instability, associating with oncogenesis. In this study, we identified that heparanase (HPSE) was localized on MTOC in mitotic cells. Induced expression of HPSE in human airway epithelial cells promoted mitotic spindle formation, and silencing of HPSE expression disrupted the mitotic spindle formation, resulting in chromosome instability, including chromosome mis-segregation and increased micronuclei formation...
April 2018: DNA and Cell Biology
Rong-Rui Wei, Dan-Ni Sun, Hong Yang, Juan Yan, Xiong Zhang, Xing-Ling Zheng, Xu-Hong Fu, Mei-Yu Geng, Xun Huang, Jian Ding
Aggregated metastatic cancer cells, referred to as circulating tumor cell (CTC) clusters, are present in the blood of cancer patients and contribute to cancer metastasis. However, the origin of CTC clusters, especially intravascular aggregates, remains unknown. Here, we employ suspension culture methods to mimic CTC cluster formation in the circulation of breast cancer patients. CTC clusters generated using these methods exhibited an increased metastatic potential that was defined by the overexpression of heparanase (HPSE)...
February 8, 2018: Acta Pharmacologica Sinica
Charmaine J Simeonovic, Sarah K Popp, Lora M Starrs, Debra J Brown, Andrew F Ziolkowski, Barbara Ludwig, Stefan R Bornstein, J Dennis Wilson, Alberto Pugliese, Thomas W H Kay, Helen E Thomas, Thomas Loudovaris, Fui Jiun Choong, Craig Freeman, Christopher R Parish
Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells in pancreatic islets are progressively destroyed. Clinical trials of immunotherapies in recently diagnosed T1D patients have only transiently and partially impacted the disease course, suggesting that other approaches are required. Our previous studies have demonstrated that heparan sulfate (HS), a glycosaminoglycan conventionally expressed in extracellular matrix, is present at high levels inside normal mouse beta cells. Intracellular HS was shown to be critical for beta cell survival and protection from oxidative damage...
2018: PloS One
Nicholas P Farrell, Anil K Gorle, Erica J Peterson, Susan J Berners-Price
Glycosaminoglycans (GAGs) such as heparin and heparan sulfate (HS) are large complex carbohydrate molecules that bind to a wide variety of proteins and exercise important physiological and pathological processes. This chapter focuses on the concept of metalloglycomics and reviews the structure and conformation of GAGs and the role of various metal ions during the interaction of GAGs with their biological partners such as proteins and enzymes. The use of metal complexes in heparin analysis is discussed. Cleavage of heparan sulfate proteoglycans (HSPGs) by the enzyme heparanase modulates tumor-related events including angiogenesis, cell invasion, metastasis, and inflammation...
February 5, 2018: Metal Ions in Life Sciences
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