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Heparanase

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https://www.readbyqxmd.com/read/28627391/low-molecular-weight-fucoidan-and-its-fractions-inhibit-renal-epithelial-mesenchymal-transition-induced-by-tgf-%C3%AE-1-or-fgf-2
#1
Xinpeng Li, Xiaohong Li, Quanbin Zhang, Tingting Zhao
We investigated the renal protective effects of low molecular weight fucoidan (LMWF) and its two fractions (F0.5 and F1.0), which were extracted from Laminaria japonica, on the epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) in HK-2 human renal proximal tubular cells. Cell morphology and EMT markers (fibronectin and alpha-smooth muscle actin) demonstrated that cells treated with TGF-β1 or FGF-2 developed EMT to a significant extent...
June 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28581485/activity-based-probes-for-functional-interrogation-of-retaining-%C3%AE-glucuronidases
#2
Liang Wu, Jianbing Jiang, Yi Jin, Wouter W Kallemeijn, Chi-Lin Kuo, Marta Artola, Wei Dai, Cas van Elk, Marco van Eijk, Gijsbert A van der Marel, Jeroen D C Codée, Bogdan I Florea, Johannes M F G Aerts, Herman S Overkleeft, Gideon J Davies
Humans express at least two distinct β-glucuronidase enzymes that are involved in disease: exo-acting β-glucuronidase (GUSB), whose deficiency gives rise to mucopolysaccharidosis type VII, and endo-acting heparanase (HPSE), whose overexpression is implicated in inflammation and cancers. The medical importance of these enzymes necessitates reliable methods to assay their activities in tissues. Herein, we present a set of β-glucuronidase-specific activity-based probes (ABPs) that allow rapid and quantitative visualization of GUSB and HPSE in biological samples, providing a powerful tool for dissecting their activities in normal and disease states...
June 5, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28581441/nk-cell-heparanase-controls-tumor-invasion-and-immune-surveillance
#3
Eva M Putz, Alyce J Mayfosh, Kevin Kos, Deborah S Barkauskas, Kyohei Nakamura, Liam Town, Katharine J Goodall, Dean Y Yee, Ivan Kh Poon, Nikola Baschuk, Fernando Souza-Fonseca-Guimaraes, Mark D Hulett, Mark J Smyth
NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA)...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28571915/3d-spheroids-what-can-they-tell-us-about-pancreatic-ductal-adenocarcinoma-cell-phenotype
#4
Nicoletta Gagliano, Chiarella Sforza, Michele Sommariva, Alessandra Menon, Vincenzo Conte, Patrizia Sartori, Patrizia Procacci
We aimed at analyzing the effect of the 3D-arrangement on the expression of some genes and proteins which play a key role in pancreatic adenocarcinoma (PDAC) progression in HPAF-II, HPAC and PL45 PDAC cells cultured in either 2D-monolayers or 3D-spheroids. Cytokeratins 7, 8, 18, 19 were differently expressed in 3D-spheroids compared to 2D-monolayers. Syndecan 1 was upregulated in HPAF-II and PL45 3D-spheroids, and downregulated in HPAC. Heparanase mRNA levels were almost unchanged in HPAF-II, and increased in HPAC and PL45 3D-spheroids...
May 29, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28571003/bptf-inhibits-nk-cell-activity-and-the-abundance-of-natural-cytotoxicity-receptor-co-ligands
#5
Kimberly Mayes, Zeinab Elsayed, Aiman Alhazmi, Michael Waters, Suehyb G Alkhatib, Mark Roberts, Carolyn Song, Kristen Peterson, Vivian Chan, Nikhil Ailaney, Pumoli Malapati, Tana Blevins, Berislav LisniÄ, Catherine I Dumur, Joseph W Landry
Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in the tumor microenvironment (TME). In culture, BPTF suppresses direct natural cytotoxicity receptor (NCR) mediated NK cell cytolytic activity to mouse and human cancer cell lines, demonstrating conserved functions. Blocking mouse NCR1 in vivo rescues BPTF KD tumor weights, demonstrating its importance for the control of tumor growth...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28569922/thrombin-is-a-selective-inducer-of-heparanase-release-from-platelets-and-granulocytes-via-protease-activated-receptor-1
#6
Mifleh Tatour, Ma'anit Shapira, Elena Axelman, Shourouk Ghanem, Anat Keren-Politansky, Lilach Bonstein, Benjamin Brenner, Yona Nadir
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. Platelets and granulocytes contain abundant amounts of heparanase that may enhance the coagulation system upon discharge. It was the aim of this study to identify the inducer and pathway of heparanase release from these cells. Platelets and granulocytes were purified from pooled normal plasma and were incubated with ATP, ADP, epinephrine, collagen, ristocetin, arachidonic acid, serotonin, LPS and thrombin...
June 1, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28560389/elemene-inhibits-the-migration-and-invasion-of-4t1-murine-breast-cancer-cells-via-heparanase
#7
Yi Zhang, Xu Sun, Nan Nan, Ke-Xin Cao, Cong Ma, Guo-Wang Yang, Ming-Wei Yu, Lin Yang, Jin-Ping Li, Xiao-Min Wang, Gan-Lin Zhang
Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad‑spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo‑D‑glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28521475/microrna-1258-an-invasion-and-metastasis-regulator-that-targets-heparanase-in-gastric-cancer
#8
Jinxin Shi, Ping Chen, Jingxu Sun, Yongxi Song, Bin Ma, Peng Gao, Xiaowan Chen, Zhenning Wang
Numerous microRNAs (miRNAs/miRs) are involved in suppressing or promoting the formation of cancer. However, to the best of our knowledge, the role of miRNA-1258 in gastric cancer (GC) has not previously been investigated. Our previous study demonstrated an increased expression of heparanase (HPSE) in GC tissues and HPSE-facilitated invasion and metastasis of GC cells. Consequently, in the present study, the function of miR-1258 in the invasion and metastasis of GC cells was investigated to determine whether miR-1258 is associated with GC through HPSE...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521428/significance-of-heparanase-in-metastatic-lymph-nodes-of-cervical-squamous-cell-cancer
#9
Bin Hu, Qing Wang, Yingying Shi, Shufang Lu, Hongjie Qu, Lu Wang, Jinquan Cui
The aim of this study was to explore the expression of heparanase (HPA) in metastatic lymph nodes (LNs) of cervical cancer and to evaluate HPA as a marker of micro-metastasis of LNs. Immunohistochemistry was performed to detect the expression of HPA in 53 cases with metastasis of LNs (group A) and 49 cases without (group B). Scoring was determined based on the intensity of immunostaining and the size of the staining area. Three points or higher score was considered as positive. Among all cases, the positive rate of HPA was 76...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28505136/gubenyiliu-ii-inhibits-breast-tumor-growth-and-metastasis-associated-with-decreased-heparanase-expression-and-phosphorylation-of-erk-and-akt-pathways
#10
Yi Zhang, Gan-Lin Zhang, Xu Sun, Ke-Xin Cao, Ya-Wen Shang, Mu-Xin Gong, Cong Ma, Nan Nan, Jin-Ping Li, Ming-Wei Yu, Guo-Wang Yang, Xiao-Min Wang
Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII...
May 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28498476/effects-of-unfractionated-heparin-and-rivaroxaban-on-the-expression-of-heparanase-and-fibroblast-growth-factor-2-in-human-osteoblasts
#11
Jingjun Xia, Wei Sheng, Liubao Pei, Ning Li, Zhipeng Zhang, Jialiang Wang, Jianing Zu, Nanxiang Wang, Duanyang Wang
Long-term treatment with anticoagulants may contribute to osteoporosis. Although unfractionated heparin and rivaroxaban have adverse effects on bone microstructure and function in adult rats, the underlying mechanism remains to be elucidated. Heparanase (HPSE) and fibroblast growth factor (FGF)2 are important signals in bone formation and fracture healing. Therefore, the present study was designed to investigate the effects of unfractionated heparin and rivaroxaban on the expression of HPSE and FGF2 in human osteoblasts...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28490587/heparanase-upregulation-contributes-to-porcine-reproductive-and-respiratory-syndrome-virus-release
#12
Chunhe Guo, Zhenbang Zhu, Yang Guo, Xiaoying Wang, Piao Yu, Shuqi Xiao, Yaosheng Chen, Yongchang Cao, Xiaohong Liu
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause substantial economic losses to the pig industry worldwide. Heparan sulfate (HS) is used by PRRSV for initial attachment to target cells. However, the role of HS in the late phase of PRRSV infection and the mechanism of virus release from host cells remain largely unknown. In this study, we showed that PRRSV infection caused a decrease of HS expression and upregulated heparanase, the only known enzyme capable to degrade HS. We subsequently demonstrated that the NF-κB signaling pathway and cathepsin L protease were involved in regulation of PRRSV infection-induced heparanase...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28486399/assessment-of-heparanase-mediated-angiogenesis-using-microvascular-endothelial-cells-identification-of-%C3%AE-carrageenan-derivative-as-a-potent-anti-angiogenic-agent
#13
Nicolas Poupard, Pamela Badarou, Fabienne Fasani, Hugo Groult, Nicolas Bridiau, Frédéric Sannier, Stéphanie Bordenave-Juchereau, Claudine Kieda, Jean-Marie Piot, Catherine Grillon, Ingrid Fruitier-Arnaudin, Thierry Maugard
Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent heparanase inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective heparanase inhibitor with an IC50 of 7...
May 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28453727/endothelial-glycocalyx-breakdown-is-mediated-by-angiopoietin-2
#14
Alexander Lukasz, Carina Hillgruber, Hans Oberleithner, Kristina Kusche-Vihrog, Hermann Pavenstädt, Alexandros Rovas, Bettina Hesse, Tobias Goerge, Philipp Kümpers
Aims: The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal surface of the endothelium, provides a first vasoprotective barrier against vascular leakage and adhesion in sepsis and vessel inflammation. Angiopoietin-2 (Angpt-2), an antagonist of the endothelium-stabilizing receptor Tie2 secreted by endothelial cells, promotes vascular permeability through cellular contraction and junctional disintegration. We hypothesized that Angpt-2 might also mediate the breakdown of the eGC...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28451171/antiangiogenic-platinum-through-glycan-targeting
#15
Erica J Peterson, A Gerard Daniel, Samantha J Katner, Lisa Bohlmann, Chih-Wei Chang, Anna Bezos, Christopher R Parish, Mark von Itzstein, Susan J Berners-Price, Nicholas P Farrell
Heparan sulfate is identified as a ligand receptor for polynuclear platinum anti-cancer agents through sulfate cluster binding. We present a new biological role for platinum and coordination compounds and a new target for metal-based drugs while presenting a new chemotype for heparanase and growth factor inhibition through modulation (metalloshielding) of their interactions. Masking of extracellular (ECM)-resident heparan sulfate (HS) through metalloshielding results in very effective inhibition of physiologically critical HS functions including enzyme (heparanase, HPSE) and protein growth factor recognition...
January 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28446717/gemcitabine-induced-heparanase-promotes-aggressiveness-of-pancreatic-cancer-cells-via-activating-egfr-signaling
#16
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-the-heparanase-procoagulant-domain-in-bleeding-and-wound-healing
#17
Y Crispel, S Ghanem, J Attias, I Kogan, B Brenner, Y Nadir
Essentials Heparanase forms a complex with tissue factor and enhances the generation of factor Xa. The present study was aimed to identify the procoagulant domain of heparanase. Procoagulant peptides significantly shortened bleeding time and enhanced wound healing. Tissue factor pathway inhibitor (TFPI)-2 derived peptides inhibited the procoagulant peptides. SUMMARY: Background Heparanase, which is known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of activated factor X (FXa)...
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
#18
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
#19
M Hao, R Franqui-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
No abstract text is available yet for this article.
April 25, 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
#20
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0160074.].
2017: PloS One
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