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March 9, 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-╬▓-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...
March 7, 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...
February 12, 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
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
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
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...
February 28, 2018: Cancer Letters
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
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
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...
January 2018: Trends in Biochemical Sciences
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
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
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...
January 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
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...
February 2018: European Journal of Haematology
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