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Heparanase

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https://www.readbyqxmd.com/read/29290138/heparan-sulfate-proteoglycans-as-relays-of-neuroinflammation
#1
Paul O'Callaghan, Xiao Zhang, Jin-Ping Li
Heparan sulfate proteoglycans (HSPGs) are implicated as inflammatory mediators in a variety of settings, including chemokine activation, which is required to recruit circulating leukocytes to infection sites. Heparan sulfate (HS) polysaccharide chains are highly interactive and serve co-receptor roles in multiple ligand:receptor interactions. HS may also serve as a storage depot, sequestering ligands such as cytokines and restricting their access to binding partners. Heparanase, through its ability to fragment HS chains, is a key regulator of HS function and has featured prominently in studies of HS's involvement in inflammatory processes...
November 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29226146/heparanase-inhibition-reduces-glucose-levels-blood-pressure-and-oxidative-stress-in-apolipoprotein-e-knockout-mice
#2
Shadi Hamoud, Rabia Shekh Muhammad, Niroz Abu-Saleh, Ahmad Hassan, Yaniv Zohar, Tony Hayek
Background: Atherosclerosis is a multifactorial process. Emerging evidence highlights a role of the enzyme heparanase in various disease states, including atherosclerosis formation and progression. Objective: The aim of the study was to investigate the effect of heparanase inhibition on blood pressure, blood glucose levels, and oxidative stress in apoE-/- mice. Methods: Male apoE-/- mice were divided into two groups: one treated by the heparanase inhibitor PG545, administered intraperitoneally weekly for seven weeks, and the other serving as control group (injected with saline)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29225052/supersulfated-low-molecular-weight-heparin-synergizes-with-igf1r-ir-inhibitor-to-suppress-synovial-sarcoma-growth-and-metastases
#3
Giuliana Cassinelli, Laura Dal Bo, Enrica Favini, Denis Cominetti, Sabina Pozzi, Monica Tortoreto, Michelandrea De Cesare, Daniele Lecis, Eugenio Scanziani, Lucia Minoli, Annamaria Naggi, Israel Vlodavsky, Nadia Zaffaroni, Cinzia Lanzi
Synovial sarcoma (SS) is an aggressive tumor with propensity for lung metastases which significantly impact patients' prognosis. New therapeutic approaches are needed to improve treatment outcome. Targeting the heparanase/heparan sulfate proteoglycan system by heparin derivatives which act as heparanase inhibitors/heparan sulfate mimetics is emerging as a therapeutic approach that can sensitize the tumor response to chemotherapy. We investigated the therapeutic potential of a supersulfated low molecular weight heparin (ssLMWH) in preclinical models of SS...
December 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29216941/-impact-of-unfractionated-heparin-on-serum-and-liver-tissue-expression-of-heparanase-in-the-liver-injury-of-mice-with-sepsis
#4
Ziwei Hu, Xiaojuan Zhang, Song Chen, Ran Zhu, Xiaochun Ma
OBJECTIVE: To investigate the effect of unfractionated heparin on the expression of serum and liver tissue heparanase (HPA) in mice with liver injury induced by sepsis. METHODS: Forty-eight healthy male C57BL/6 mice aged 6-8 weeks were divided into groups according to random number table method. Twenty-four septic mice models (CLP group) were established by cecal ligation and puncture (CLP); the other 24 mice underwent sham operation (sham group), only laparotomy and abdominal closure were performed without ligation...
December 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29209837/emerging-enzymatic-targets-controlling-angiogenesis-in-cancer-preclinical-evidence-and-potential-clinical-applications
#5
REVIEW
Biagio Ricciuti, Jennifer Foglietta, Rita Chiari, Amirhossein Sahebkar, Maciej Banach, Vanessa Bianconi, Matteo Pirro
Angiogenesis has always been considered as a fundamental therapeutic target for inhibiting tumor growth and metastasis. To date, anti-angiogenic treatments that have been approved are principally based on either administration of monoclonal antibodies targeting the vascular endothelial growth factor/vascular endothelial growth factor receptor axis or multikinase inhibitors. However, a growing body of evidence is pointing out the role of different classes of enzymes involved in tumor-driven angiogenesis, whose inhibition in preclinical models has already shown encouraging results...
December 4, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29162390/opposing-functions-of-heparanase-1-and-heparanase-2-in-cancer-progression
#6
REVIEW
Israel Vlodavsky, Miriam Gross-Cohen, Marina Weissmann, Neta Ilan, Ralph D Sanderson
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 regulating the bioavailability of heparin-binding proteins; priming the tumor microenvironment; mediating tumor-host crosstalk; and inducing gene transcription, signaling pathways, exosome formation, and autophagy that together promote tumor cell performance and chemoresistance...
November 18, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29158804/heparanase-contributes-to-trans-endothelial-migration-of-hepatocellular-carcinoma-cells
#7
Xiaopeng Chen, Wen Jiang, Chaofu Yue, Wenjun Zhang, Chaogang Tong, Dafei Dai, Bin Cheng, Chen Huang, Linming Lu
The overall outcome of patients with hepatocellular carcinoma (HCC) is still very poor due to its high metastasis and recurrence rate. During metastasis, trans-endothelial migration (TEM) of HCC cells is a key step. Heparanase (HPSE) is an endo-beta-glucuronidase and exerts prometastatic properties for normal and tumor-derived cells. However, it is remains unclear that HPSE contributes to TEM of HCC cells. In this study, human umbilical vein endothelial cells-C (HUVEC-C) was used to simulate vascular endothelial cells (VECs), and the HCCLM3 cells with high HPSE expression were chosen and used for in vitro TEM assay and in vivo experiment...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158323/fgf8-morphogen-gradients-are-differentially-regulated-by-heparan-sulphotransferases-hs2st-and-hs6st1-in-the-developing-brain
#8
Wai-Kit Chan, David J Price, Thomas Pratt
Fibroblast growth factor (FGF) morphogen signalling through the evolutionarily ancient Extracellular signaling Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) pathway recurs in many neural and non-neural developmental contexts and understanding the mechanisms that regulate FGF/ERK function are correspondingly important. The glycosaminoglycan heparan sulphate (HS) binds to FGFs and exists in an enormous number of differentially sulphated forms produced by the action of HS modifying enzymes so has the potential to present an extremely large amount of information in FGF/ERK signalling...
November 20, 2017: Biology Open
https://www.readbyqxmd.com/read/29153700/heparanase-expression-in-blood-is-sensitive-to-monitor-response-to-anticancer-treatment-in-pancreatic-cancer-a-pilot-study
#9
Wujun Wu, Lin Zhao, Yongtian Yu, Haitian Hu, Huaiping Shi, Qian'an Jia, Lixue Du
BACKGROUND: /Objectives: High heparanase level was shown in maliganant tumor; however, whether or not heparanase may serve as a sensitive marker to monitor response to anticancer treatment is still unknown. METHODS: In the pilot study, heparanase mRNA expression in peripheral blood mononuclear cell fraction (PBMC) and activity in plasma and urine were detected by quantitative real time RT-PCR and heparan-degrading enzyme assay in 31 pancreatic cancer patients. RESULTS: Heparanase mRNA and activity in samples from cancer patients were significantly higher than that in healthy donors...
November 13, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29120525/heparanase-level-and-procoagulant-activity-are-reduced-in-severe-sepsis
#10
Moshe Matan, Daniel King, Eli Peled, Shanny Ackerman, Yaron Bar-Lavi, Benjamin Brenner, Yona Nadir
BACKGROUND: During severe sepsis, levels and activity of all coagulation proteins are reduced. Heparanase is implicated in angiogenesis and tumor progression. We previously demonstrated that heparanase also affected the hemostatic system. It forms a complex and increases the activity of the blood coagulation initiator tissue factor. AIM: To evaluate heparanase levels and procoagulant activity as predictors of sepsis severity. MATERIALS AND METHODS: Twenty one patients with non-trauma, non-surgical sepsis admitted to the Intensive Care Unit and 35 controls were recruited...
November 9, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29106944/proteases-and-glycosidases-on-the-surface-of-exosomes-newly-discovered-mechanisms-for-extracellular-remodeling
#11
REVIEW
Ralph D Sanderson, Shyam K Bandari, Israel Vlodavsky
Emergence of the field of exosome biology has opened an exciting door to better understand communication between cells. These tiny nanovesicles act as potent regulators of biological function by delivering proteins, lipids and nucleic acids from the cell of origin to target cells. Recently, several enzymes including membrane-type 1 matrix metalloproteinase (MT1-MMP), insulin-degrading enzyme (IDE), sialidase and heparanase, among others, were localized on the surface of exosomes secreted by various cell types...
October 26, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29104277/heparan-sulfate-biosynthetic-system-is-inhibited-in-human-glioma-due-to-ext1-2-and-hs6st1-2-down-regulation
#12
Victor S Ushakov, Alexandra Y Tsidulko, Gabin de La Bourdonnaye, Galina M Kazanskaya, Alexander M Volkov, Roman S Kiselev, Vyacheslav V Kobozev, Diana V Kostromskaya, Alexey S Gaytan, Alexei L Krivoshapkin, Svetlana V Aidagulova, Elvira V Grigorieva
Heparan sulfate (HS) is an important component of the extracellular matrix and cell surface, which plays a key role in cell-cell and cell-matrix interactions. Functional activity of HS directly depends on its structure, which determined by a complex system of HS biosynthetic enzymes. During malignant transformation, the system can undergo significant changes, but for glioma, HS biosynthesis has not been studied in detail. In this study, we performed a comparative analysis of the HS biosynthetic system in human gliomas of different grades...
November 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29097791/heparanase-and-macrophage-interplay-in-the-onset-of-liver-fibrosis
#13
Maria Francesca Secchi, Marika Crescenzi, Valentina Masola, Francesco Paolo Russo, Annarosa Floreani, Maurizio Onisto
The heparan sulfate endoglycosidase heparanase (HPSE) is involved in tumor growth, chronic inflammation and fibrosis. Since a role for HPSE in chronic liver disease has not been demonstrated to date, the current study was aimed at investigating the involvement of HPSE in the pathogenesis of chronic liver injury. Herein, we revealed that HPSE expression increased in mouse livers after carbon tetrachloride (CCl4)-mediated chronic induction of fibrosis, but with a trend to decline during progression of the disease...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29066725/heparan-sulfate-resilience-factor-and-therapeutic-target-for-cocaine-abuse
#14
Jihuan Chen, Tomoya Kawamura, Manveen K Sethi, Joseph Zaia, Vez Repunte-Canonigo, Pietro Paolo Sanna
Substance abuse is a pressing problem with few therapeutic options. The identification of addiction resilience factors is a potential strategy to identify new mechanisms that can be targeted therapeutically. Heparan sulfate (HS) is a linear sulfated polysaccharide that is a component of the cell surface and extracellular matrix. Heparan sulfate modulates the activity and distribution of a set of negatively charged signaling peptides and proteins - known as the HS interactome - by acting as a co-receptor or alternative receptor for growth factors and other signaling peptides and sequestering and localizing them, among other actions...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29037916/pfaffia-paniculata-brazilian-ginseng-extract-modulates-mapk-and-mucin-pathways-in-intestinal-inflammation
#15
C A R A Costa, A E V Quaglio, L C Di Stasi
ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia paniculata is an endemic Brazilian plant traditionally used against fatigue, stress, inflammation and low immune system as well as with proven intestinal anti-inflammatory activity. AIM OF THE STUDY: To evaluate intestinal anti-inflammatory effects of P. paniculata on the mRNA abundance of Hsp70, Heparanase, Mapk1, Mapk3, Mapk6, Mapk9, Muc1, Muc2, Muc3, Muc4, and NF-κB, as well as the mucin content in colonic samples. MATERIAL AND METHODS: Intestinal inflammation was induced by TNBS and rats were divided into groups that received vehicle or 25, 50, 100, or 200mg/kg of P...
October 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28994624/plasma-heparanase-is-associated-with-blood-glucose-levels-but-not-urinary-microalbumin-excretion-in-type-2-diabetic-nephropathy-at-the-early-stage
#16
Yue Zhao, Jingshun Liu, Shichao Ten, Jisheng Zhang, Yanggang Yuan, Jiangyi Yu, Xiaofei An
AIM: To explore the possible correlations between plasma heparanase and albuminuria, glucose and lipid metabolism in the type 2 diabetic nephropathy patients at the early stage. METHODS: One hundred and forty patients with type 2 diabetic nephropathy at early stage were recruited into the study. Plasma heparanase and the characterized advanced glycation end products (AGEs), carboxymethyllysine (CML) were measured by enzyme-linked immunosorbent assay. RESULTS: Plasma heparanase was positively associated with fasting blood glucose (R = 0...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28986359/dual-effects-of-hyperglycemia-on-endothelial-cells-and-cardiomyocytes-to-enhance-coronary-lpl-activity
#17
Amy Pei-Ling Chiu, Denise Bierende, Nathaniel Lal, Fulong Wang, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodriges
In the diabetic heart, there is excessive dependence on FA utilization to generate ATP. Lipoprotein lipase (LPL)-mediated hydrolysis of circulating triglyceride (TG) is suggested to be the predominant source of FA for cardiac utilization during diabetes. In the heart, majority of LPL is synthesized in cardiomyocytes, and secreted onto cell surface heparan sulfate proteoglycans (HSPG), where an endothelial cell (EC) releasable β-endoglycosidase, heparanase, cleaves the side chains of HSPG to liberate LPL for its onward movement across the EC...
October 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28981558/association-of-polymorphisms-in-the-heparanase-gene-hpse-with-hepatocellular-carcinoma-in-chinese-populations
#18
Lixia Yu, Xiaoai Zhang, Yun Zhai, Hongxing Zhang, Wei Yue, Xiumei Zhang, Zhifu Wang, Hong Zhou, Gangqiao Zhou, Feng Gong
Heparanase activity is involved in cancer growth and development in humans and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be associated with tumors. In this study, we investigated whether SNPs in HPSE were a risk factor for hepatocellular carcinoma (HCC) by undertaking a comprehensive haplotype-tagging, case-control study. For this, six haplotype-tagging SNPs (htSNPs) in HPSE were genotyped in 400 HCC patients and 480 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis...
October 2, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28980126/expression-of-prl-3-regulates-proliferation-and-invasion-of-breast-cancer-cells-in-vitro
#19
Isabel Radke, Martin Götte, Martin Smollich, Ninette Scharle, Ludwig Kiesel, Pia Wülfing
PURPOSE: The protein tyrosine phosphatase PRL-3 plays an important role in cancer cell migration, invasion and metastasis. In breast cancer, PRL-3 is overexpressed in 70-75% of tumors and even more frequently in lymph node metastases. Moreover, PRL-3 overexpression in breast cancer is associated with an adverse disease outcome. Aim of this study was to determine the role of PRL-3 in breast cancer cell proliferation, migration and invasion in vitro. METHODS: PRL-3 mRNA expression was evaluated in 6 breast cancer cell lines by quantitative real-time PCR...
October 4, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28974047/heparin-mimetics-their-therapeutic-potential
#20
REVIEW
Shifaza Mohamed, Deirdre R Coombe
Heparin mimetics are synthetic and semi-synthetic compounds that are highly sulfated, structurally distinct analogues of glycosaminoglycans. These mimetics are often rationally designed to increase potency and binding selectivity towards specific proteins involved in disease manifestations. Some of the major therapeutic arenas towards which heparin mimetics are targeted include: coagulation and thrombosis, cancers, and inflammatory diseases. Although Fondaparinux, a rationally designed heparin mimetic, is now approved for prophylaxis and treatment of venous thromboembolism, the search for novel anticoagulant heparin mimetics with increased affinity and fewer side effects remains a subject of research...
October 2, 2017: Pharmaceuticals
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