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https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#1
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27890389/heparanase-confers-a-growth-advantage-to-differentiating-murine-embryonic-stem-cells-and-enhances-oligodendrocyte-formation
#2
Anqi Xiong, Soumi Kundu, Maud Forsberg, Yuyuan Xiong, Tobias Bergström, Tanja Paavilainen, Lena Kjellén, Jin-Ping Li, Karin Forsberg-Nilsson
Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage...
November 23, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27886097/investigating-glycol-split-heparin-derived-inhibitors-of-heparanase-a-study-of-synthetic-trisaccharides
#3
Minghong Ni, Stefano Elli, Annamaria Naggi, Marco Guerrini, Giangiacomo Torri, Maurice Petitou
Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS (1) and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (2) from glucose...
November 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27878294/arctigenin-a-lignan-from-arctium-lappa-l-inhibits-metastasis-of-human-breast-cancer-cells-through-the-downregulation-of-mmp-2-9-and-heparanase-in-mda-mb-231-cells
#4
Chenghua Lou, Zhihui Zhu, Yaping Zhao, Rui Zhu, Huajun Zhao
Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L. which has been widely used as a diuretic and a diaphoretic in Traditional Chinese Medicine. In the present study, the authors investigated the effects of arctigenin on tumor migration and invasion in aggressive human breast cancer cells. The MTT assay results showed that arctigenin did not show a significant cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound healing migration and Boyden chamber invasion assays demonstrated that arctigenin significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells...
November 23, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27853671/heparanase-inhibitors-facilitate-the-assembly-of-the-basement-membrane-in-artificial-skin
#5
Makoto Tsunenaga
Recent research suggests that the basement membrane at the dermal-epidermal junction of the skin plays an important role in maintaining a healthy epidermis and dermis, and repeated damage to the skin can destabilize the skin and accelerate the aging process. Skin-equivalent models are suitable for studying the reconstruction of the basement membrane and its contribution to epidermal homeostasis because they lack the basement membrane and show abnormal expression of epidermal differentiation markers. By using these models, it has been shown that reconstruction of the basement membrane is enhanced not only by supplying basement membrane components, but also by inhibiting proteinases such as urokinase and matrix metalloproteinase...
August 2016: Current Tissue Engineering
https://www.readbyqxmd.com/read/27849593/heparanase-is-required-for-activation-and-function-of-macrophages
#6
Lilach Gutter-Kapon, Dror Alishekevitz, Yuval Shaked, Jin-Ping Li, Ami Aronheim, Neta Ilan, Israel Vlodavsky
The emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized and is encouraging the development of heparanase inhibitors as anticancer drugs. Unlike the function of heparanase in cancer cells, very little attention has been given to heparanase contributed by cells composing the tumor microenvironment. Here we used a genetic approach and examined the behavior and function of macrophages isolated from wild-type (WT) and heparanase-knockout (Hpa-KO) mice. Hpa-KO macrophages express lower levels of cytokines (e...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27842848/structural-features-of-heparanase-inhibiting-non-anticoagulant-heparin-derivative-roneparstat
#7
Anna Alekseeva, Giulia Mazzini, Giuseppe Giannini, Annamaria Naggi
Owing to their anti-tumor and anti-inflammatory properties, non-anticoagulant glycol-split (gs) heparins, obtained by periodate oxidation/borohydride reduction, are of growing interest. The present study was focused on the structural characterization of N-acetylated gs-heparin Roneparstat, a promising anti-cancer heparanase-inhibiting drug currently being investigated in clinical trials. The major and minor structural features of structurally complex Roneparstat have been characterized for the first time using conductimetric titration, size-exclusion chromatography with triple detector array, NMR and LC/MS...
January 20, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27828631/expression-of-heparanase-in-basal-cell-carcinoma-and-squamous-cell-carcinoma
#8
Maria Aparecida Silva Pinhal, Maria Carolina Leal Almeida, Alessandra Scorse Costa, Thérèse Rachell Theodoro, Rodrigo Lorenzetti Serrano, Carlos D'Apparecida Santos Machado
Background: Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives: Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control)...
September 2016: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/27804885/the-functions-of-heparanase-in-human-diseases
#9
Hao Jin, Shaobo Zhou
The study of the heparanase has long been paid wide attention. Heparanase ,an endo-β-D-glucuronidase, is capable of specifically degrading heparan sulfate(HS), one of the excellular matrix(ECM) components. It exerts its enzymatic activity catalyzing the cleavage of the β (1,4)-glycosidic bond between glucuronic acid and glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion...
November 1, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27784443/-the-expression-and-significance-of-heparanase-in-oral-squamous-cell-carcinoma-with-different-metastatic-potentials
#10
X B Wu, R Y Wang, Z J Gong, J Yu, S R Zhu
Objective: To detect the expression of heparanase (HPSE) in oral squamous cell carcinoma (OSCC) with different metastatic potentials and investigate its clinical significance. Methods: Transcriptional and translational status of HPSE in OSCC cell lines with different metastatic capacities, primary OSCC samples and their paired metastatic cancer tissues were determined using real-time polymerase chain reaction (PCR) and Western blotting analysis. Immunohistochemistry was used to evaluate HPSE expression in 131 OSCC samples...
October 18, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27783948/macrophage-induced-lymphangiogenesis-and-metastasis-following-paclitaxel-chemotherapy-is-regulated-by-vegfr3
#11
Dror Alishekevitz, Svetlana Gingis-Velitski, Orit Kaidar-Person, Lilach Gutter-Kapon, Sandra D Scherer, Ziv Raviv, Emmanuelle Merquiol, Yael Ben-Nun, Valeria Miller, Chen Rachman-Tzemah, Michael Timaner, Yelena Mumblat, Neta Ilan, David Loven, Dov Hershkovitz, Ronit Satchi-Fainaro, Galia Blum, Jonathan P Sleeman, Israel Vlodavsky, Yuval Shaked
While chemotherapy strongly restricts or reverses tumor growth, the response of host tissue to therapy can counteract its anti-tumor activity by promoting tumor re-growth and/or metastases, thus limiting therapeutic efficacy. Here, we show that vascular endothelial growth factor receptor 3 (VEGFR3)-expressing macrophages infiltrating chemotherapy-treated tumors play a significant role in metastasis. They do so in part by inducing lymphangiogenesis as a result of cathepsin release, leading to VEGF-C upregulation by heparanase...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27758044/heparanase-regulation-of-cancer-autophagy-and-inflammation-new-mechanisms-and-targets-for-therapy
#12
REVIEW
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 nonenzymatic mechanisms that directly activate signaling at the cell surface...
October 18, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27741490/corrigendum-to-recent-advances-in-the-discovery-of-heparanase-inhibitors-as-anti-cancer-agents-eur-j-mech-121-2016-209-220
#13
Li Jia, Shutao Ma
No abstract text is available yet for this article.
October 11, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27732945/the-prognostic-significance-of-heparanase-expression-in-metastatic-melanoma
#14
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
https://www.readbyqxmd.com/read/27711215/heparanase-overexpression-reduces-hepcidin-expression-affects-iron-homeostasis-and-alters-the-response-to-inflammation
#15
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
https://www.readbyqxmd.com/read/27685626/mirna-558-promotes-gastric-cancer-progression-through-attenuating-smad4-mediated-repression-of-heparanase-expression
#16
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
https://www.readbyqxmd.com/read/27666777/the-heparanase-heparan-sulfate-proteoglycan-axis-a-potential-new-therapeutic-target-in-sarcomas
#17
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
https://www.readbyqxmd.com/read/27633889/harnessing-bioinformatics-for-designing-a-novel-multi-epitope-peptide-vaccine-against-breast-cancer
#18
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
https://www.readbyqxmd.com/read/27595937/smad4-suppresses-the-tumorigenesis-and-aggressiveness-of-neuroblastoma-through-repressing-the-expression-of-heparanase
#19
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
https://www.readbyqxmd.com/read/27585841/fluorescent-molecular-imaging-of-metastatic-lymph-node-using-near-infrared-emitting-low-molecular-weight-heparin-modified-nanoliposome-based-on-enzyme-substrate-interaction
#20
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
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