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Heparanase

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https://www.readbyqxmd.com/read/28446717/gemcitabine-induced-heparanase-promotes-aggressiveness-of-pancreatic-cancer-cells-via-activating-egfr-signaling
#1
Jin-Wen Song, Ying-Xia Tan, Su-Bo Li, Shi-Kun Zhang, Lu-Ming Wan, Shou-Ping Ji, Hong Zhou, Zhi-Hang Zhou, Feng Gong
Pancreatic cancer (PC), characterized by aggressive local invasion and metastasis, is one of the most malignant cancers. Gemcitabine is currently used as the standard drug for the treatment of advanced and metastatic PC, but with limited efficacy. In this study, we demonstrated that gemcitabine increased the expression of heparanase (HPA1), the only known mammalian endoglycosidase capable of cleaving heparan sulfate, both in vitro and in vivo. Furthermore, overexpression of HPA1 in PC cell lines enhanced proliferation and invasion, accompanied with elevated phosphorylation of EGFR...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439967/involvement-of-heparanase-procoagulant-domain-in-bleeding-and-wound-healing
#2
Yonatan Crispel, Shourouk Ghanem, Judith Attias, Inna Kogan, Benjamin Brenner, Yona Nadir
BACKGROUND: Heparanase, known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of factor Xa. Our study demonstrated that peptides derived from TF pathway inhibitor (TFPI)-2 impeded the procoagulant effect of heparanase and attenuated inflammation, tumor growth and vascularization. AIMS: The present study aimed to identify the procoagulant domain in the heparanase molecule and to evaluate its effects in a model of wound healing that involves inflammation and angiogenesis...
April 25, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28401953/overexpression-of-heparanase-enhances-t-lymphocyte-activities-and-intensifies-the-inflammatory-response-in-a-model-of-murine-rheumatoid-arthritis
#3
Andreas Digre, Kailash Singh, Magnus Åbrink, Rogier M Reijmers, Stellan Sandler, Israel Vlodavsky, Jin-Ping Li
Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced animals developed clinical symptoms, i...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28400617/nek2-induces-osteoclast-differentiation-and-bone-destruction-via-heparanase-in-multiple-myeloma
#4
M Hao, R F Machin, H Xu, J Shaughnessy, B Barlogie, D Roodman, D E Quelle, S Janz, M H Tomasson, R D Sanderson, L Qiu, I Frech, G Tricot, F Zhan
Leukemia accepted article preview online, 12 April 2017. doi:10.1038/leu.2017.115.
April 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28394941/correction-heparanase-a-potential-new-factor-involved-in-the-renal-epithelial-mesenchymal-transition-emt-induced-by-ischemia-reperfusion-i-r-injury
#5
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0160074.].
2017: PloS One
https://www.readbyqxmd.com/read/28388549/elevated-heparanase-expression-is-associated-with-poor-prognosis-in-breast-cancer-a-study-based-on-systematic-review-and-tcga-data
#6
REVIEW
Xu Sun, Ganlin Zhang, Jiayun Nian, Mingwei Yu, Shijian Chen, Yi Zhang, Guowang Yang, Lin Yang, Peiyu Cheng, Chen Yan, Yunfei Ma, Hui Meng, Xiaomin Wang, Jin-Ping Li
Heparanase promotes tumorigenesis, angiogenesis, and metastasis. Here, we conducted a study based on systematic review and the Cancer Genome Atlas (TCGA) data that examined heparanase expression in clinical samples to determine its prognostic value. According to the meta-analysis and TCGA data, we found that heparanase expression was up-regulated in most breast cancer specimens, and elevated heparanase expression was associated with increased lymph node metastasis, larger tumor size, higher histological grade, and poor survival...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388547/involvement-of-heparanase-in-the-pathogenesis-of-acute-kidney-injury-nephroprotective-effect-of-pg545
#7
Zaid Abassi, Shadi Hamoud, Ahmad Hassan, Iyad Khamaysi, Omri Nativ, Samuel N Heyman, Rabia Shekh Muhammad, Neta Ilan, Preeti Singh, Edward Hammond, Gianluigi Zaza, Antonio Lupo, Maurizio Onisto, Gloria Bellin, Valentina Masola, Israel Vlodavsky, Giovani Gambaro
Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387673/upregulated-expression-of-heparanase-and-heparanase-2-in-the-brains-of-alzheimer-s-disease
#8
Beatriz García, Carla Martín, Olivia García-Suárez, Bárbara Muñiz-Alonso, Helena Ordiales, Santiago Fernández-Menéndez, Jorge Santos-Juanes, Laura Lorente-Gea, Sonia Castañón, Ikerne Vicente-Etxenausia, Kelvin Manuel Piña Batista, Irune Ruiz-Díaz, María Cristina Caballero-Martínez, Jesús Merayo-Lloves, Isabel Guerra-Merino, Luis M Quirós, Iván Fernández-Vega
BACKGROUND: Heparan sulfate proteoglycans (HSPGs) promote amyloid-β peptide and tau fibrillization in Alzheimer's disease (AD) and provide resistance against proteolytic breakdown. Heparanase (HPSE) is the only enzyme that cleaves heparan sulfate (HS). Heparanase 2 (HPSE2) lacks HS-degrading activity, although it is able to interact with HS with high affinity. OBJECTIVE: To analyze HPSE and HPSE2 expressions at different stages of AD. METHODS: RT-PCR was used to analyze transcription levels of both heparanases at different stages of AD, and immunohistochemistry was performed to localize each one in different parts of the brain...
April 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28386074/the-role-of-heparanase-in-the-pathogenesis-of-acute-pancreatitis-a-potential-therapeutic-target
#9
Iyad Khamaysi, Preeti Singh, Susan Nasser, Hoda Awad, Yehuda Chowers, Edmond Sabo, Edward Hammond, Ian Gralnek, Irena Minkov, Alessandro Noseda, Neta Ilan, Israel Vlodavsky, Zaid Abassi
Acute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains of HS sulfate proteoglycans into shorter oligosaccharides, activity that is highly implicated in cellular invasion associated with cancer metastasis and inflammation. Given that AP involves a strong inflammatory aspect, we examined whether heparanase plays a role in AP...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385219/production-of-heparin-and-%C3%AE-carrageenan-anti-heparanase-derivatives-using-a-combination-of-physicochemical-depolymerization-and-glycol-splitting
#10
Nicolas Poupard, Hugo Groult, Justine Bodin, Nicolas Bridiau, Stéphanie Bordenave-Juchereau, Frédéric Sannier, Jean-Marie Piot, Ingrid Fruitier-Arnaudin, Thierry Maugard
Strongly associated with tumor angiogenesis and metastasis, the enzyme heparanase is an endo-β-d-glucuronidase which is overexpressed in the tumor microenvironment. Its inhibition could be one of the most promising anti-angiogenic approaches to date. Although heparin is known as a good heparanase inhibitor, it also possesses major anticoagulant properties that may be incompatible with its use as an anti-angiogenic agent, hence the considerable interest for other sources of sulfated polysaccharides. Recent investigations point to λ-carrageenans, highly sulfated galactans with a tremendous potential that are found in red algae...
June 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28364042/kinetic-based-trapping-by-intervening-sequence-variants-of-the-active-sites-of-protein-disulfide-isomerase-identifies-platelet-protein-substrates
#11
Jack D Stopa, Katherine M Baker, Steven P Grover, Robert Flaumenhaft, Bruce Furie
Thiol isomerases such as protein disulfide isomerase (PDI) direct disulfide rearrangements required for proper folding of nascent proteins synthesized in the endoplasmic reticulum. Identifying PDI substrates is challenging since PDI catalyzes conformational changes that cannot be easily monitored (e.g., compared with proteolytic cleavage or amino acid phosphorylation), PDI has multiple substrates, and it can catalyze either oxidation, reduction, or isomerization of substrates. Kinetic-based substrate trapping wherein the active site motif CGHC is modified to CGHA to stabilize a PDI-substrate intermediate is effective in identifying some substrates...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28359266/identification-of-novel-class-of-triazolo-thiadiazoles-as-potent-inhibitors-of-human-heparanase-and-their-anticancer-activity
#12
C P Baburajeev, Chakrabhavi Dhananjaya Mohan, Shobith Rangappa, Daniel J Mason, Julian E Fuchs, Andreas Bender, Uri Barash, Israel Vlodavsky, Basappa, Kanchugarakoppal S Rangappa
BACKGROUND: Expression and activity of heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains of proteoglycans, is associated with progression and poor prognosis of many cancers which makes it an attractive drug target in cancer therapeutics. METHODS: In the present work, we report the in vitro screening of a library of 150 small molecules with the scaffold bearing quinolones, oxazines, benzoxazines, isoxazoli(di)nes, pyrimidinones, quinolines, benzoxazines, and 4-thiazolidinones, thiadiazolo[3,2-a]pyrimidin-5-one, 1,2,4-triazolo-1,3,4-thiadiazoles, and azaspiranes against the enzymatic activity of human heparanase...
March 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28351285/heparanase-overexpression-down-regulates-syndecan-1-expression-in-a-gallbladder-carcinoma-cell-line
#13
Hao Jin, Shaobo Zhou, Song Yang, Hai-Ming Cao
Objective To discuss the relevance of heparanase and syndecan-1 and regulation of the heparanase-syndecan1 axis in the invasiveness of gallbladder carcinoma cells. Methods 1. Generation of a gallbladder cancer cell line overexpressing a heparanase (GBD-SD) transgene. 2. Western blot analysis of syndecan-1 levels of GBD-SD and control gallbladder carcinoma (GBC-SD) cells. 3. RT-PCR analysis of syndecan-1 mRNA levels of GBD-SD and GBC-SD. 4. Evaluation of invasion and migration of GBD-SD and GBC-SD cells. Results 1...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28347755/inhibition-of-inflammation-induced-shedding-of-the-endothelial-glycocalyx-with-low-molecular-weight-heparin
#14
Herbert H Lipowsky, Anne Lescanic
The endothelial surface layer (ESL) consists of the endothelial cell (EC) glycocalyx and adsorbed proteins, and forms a barrier between blood and the EC. Enzymatic shedding of the ESL in response to cytokines may expose receptors for leukocyte (WBC) adhesion and increase vascular permeability. Thus, intravital microscopy was used to explore stabilization of the ESL with low molecular weight heparin (LMWH) to mitigate structural changes with inflammation. Following bolus infusions (i.v.) of LMWH (0.12-1.6mg/kg), shedding of glycans in response to 10(-7)M fMLP was measured by loss of fluorescently labeled lectins bound to the EC and WBC-EC adhesion was monitored in post-capillary venules of rat mesentery...
March 27, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28337373/heparanase-promotes-radiation-resistance-of-cervical-cancer-by-upregulating-hypoxia-inducible-factor-1
#15
Jianping Li, Xin Meng, Jing Hu, Ying Zhang, Yunzhi Dang, Lichun Wei, Mei Shi
Heparanase (HPSE1) is elevated in various types of cancers including cervical cancer, and correlated with poor prognosis. Current study is to investigate the effects of HPSE1 on radiation response in cervical cancer. Colony formation assays after radiation were performed to compare the radiation response among control, HPSE1 knockdown and HPSE1 overexpression HeLa cells. The mRNA and protein levels of HIF1, bFGF and VEGF were measured as indicators for the activity of HIF1 pathway. Xenograft mouse model were used to study the HPSE1 radiation regulator effects in vivo...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28326469/hsv-1-interaction-to-3-o-sulfated-heparan-sulfate-in-mouse-derived-drg-explant-and-profiles-of-inflammatory-markers-during-virus-infection
#16
Harsh Sharthiya, Chanmoly Seng, T H Van Kuppevelt, Vaibhav Tiwari, Michele Fornaro
The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry...
March 21, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28314760/loss-of-vegfb-and-its-signaling-in-the-diabetic-heart-is-associated-with-increased-cell-death-signaling
#17
Nathaniel Lal, Amy Pei-Ling Chiu, Fulong Wang, Dahai Zhang, Jocelyn Jia, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
VEGFB is highly expressed in metabolically active tissues, such as the heart and skeletal muscle, suggesting a function in maintaining oxidative metabolic and contractile function in these tissues. Multiple models of heart failure have indicated a significant drop in VEGFB. However, whether there is a role for decreased VEGFB in diabetic cardiomyopathy is currently unknown. Of the VEGFB located in cardiomyocytes, there is a substantial and readily releasable pool localized on the cell surface. The immediate response to high glucose and the secretion of endothelial heparanase is the release of this surface bound VEGFB, which triggers signaling pathways and gene expression to influence endothelial cell (autocrine action) and cardiomyocyte (paracrine effects) survival...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28292981/vaginal-heparan-sulfate-linked-to-neutrophil-dysfunction-in-the-acute-inflammatory-response-associated-with-experimental-vulvovaginal-candidiasis
#18
Junko Yano, Mairi C Noverr, Paul L Fidel
Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice)...
March 14, 2017: MBio
https://www.readbyqxmd.com/read/28286736/overexpression-of-heparanase-attenuated-tgf-%C3%AE-stimulated-signaling-in-tumor-cells
#19
Tahira Batool, Jianping Fang, Uri Barash, Aristidis Moustakas, Israel Vlodavsky, Jin-Ping Li
Heparan sulfate (HS) mediates the activity of various growth factors including TGF-β. Heparanase is an endo-glucuronidase that specifically cleaves and modifies HS structure. In this study, we examined the effect of heparanase expression on TGF-β1-dependent signaling activities. We found that overexpression of heparanase in human tumor cells (i.e., Fadu pharyngeal carcinoma, MCF7 breast carcinoma) attenuated TGF-β1-stimulated Smad phosphorylation and led to a slower cell proliferation. TGF-β1-stimulated Akt and Erk phosphorylation was also affected in the heparanase overexpression cells...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28284615/pyrithione-inhibits-porcine-reproductive-and-respiratory-syndrome-virus-replication-through-interfering-with-nf-%C3%AE%C2%BAb-and-heparanase
#20
Chunhe Guo, Zhenbang Zhu, Xiaoying Wang, Yaosheng Chen, Xiaohong Liu
Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pig industry, causing high economic losses worldwide. Current vaccination strategies provide only limited protection against PRRSV infection. Consequently, there is a need to develop new antiviral strategies. Pyrithione (PT), a zinc ionophore, is used as an antibacterial and antifungal agent, and evidence has shown that PT inhibits the replication of various RNA viruses. However, there is no data regarding its effects against PRRSV infection until now...
March 2017: Veterinary Microbiology
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