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https://www.readbyqxmd.com/read/28215163/targeting-heparan-sulfate-proteoglycans-and-their-modifying-enzymes-to-enhance-anticancer-chemotherapy-efficacy-and-overcome-drug-resistance
#1
Cinzia Lanzi, Nadia Zaffaroni, Giuliana Cassinelli
Targeting heparan sulfate proteoglycans (HSPGs) and enzymes involved in heparan sulfate (HS) chain editing is emerging as a new anticancer strategy. The involvement of HSPGs in tumor cell signaling, inflammation, angiogenesis and metastasis indicates that agents able to inhibit aberrant HSPG functions can potentially act as multitarget drugs affecting both tumor cell growth and the supportive boost provided by the microenvironment. Moreover, accumulating evidence supports that an altered expression or function of HSPGs, or of the complex enzyme system regulating their activities, can also depress the tumor response to anticancer treatments in several tumor types...
February 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28098909/biology-and-function-of-glypican-3-as-a-candidate-for-early-cancerous-transformation-of-hepatocytes-in-hepatocellular-carcinoma-review
#2
Mauro Montalbano, Jeremias Georgiadis, Ashlyn L Masterson, Joshua T McGuire, Janika Prajapati, Ali Shirafkan, Cristiana Rastellini, Luca Cicalese
Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome...
January 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28089430/high-variability-of-expression-profiles-of-homeologous-genes-for-wnt-hh-notch-and-hippo-signaling-pathways-in-xenopus-laevis
#3
Tatsuo Michiue, Takayoshi Yamamoto, Yuuri Yasuoka, Toshiyasu Goto, Takafumi Ikeda, Kei Nagura, Takuya Nakayama, Masanori Taira, Tsutomu Kinoshita
Cell signaling pathways, such as Wnt, Hedgehog (Hh), Notch, and Hippo, are essential for embryogenesis, organogenesis, and tissue homeostasis. In this study, we analyzed 415 genes involved in these pathways in the allotetraploid frog, Xenopus laevis. Most genes are retained in two subgenomes called L and S (193 homeologous gene pairs and 29 singletons). This conservation rate of homeologs is much higher than that of all genes in the X. laevis genome (86.9% vs 60.2%). Among singletons, 24 genes are retained in the L subgenome, a rate similar to the average for all genes (82...
January 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28068429/functional-requirements-for-heparan-sulfate-biosynthesis-in-morphogenesis-and-nervous-system-development-in-c-elegans
#4
Cassandra R Blanchette, Andrea Thackeray, Paola N Perrat, Siegfried Hekimi, Claire Y Bénard
The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/27930836/hepatitis-c-virus-infection-propagates-through-interactions-between-syndecan-1-and-cd81-and-impacts-the-hepatocyte-glycocalyx
#5
Boyan Grigorov, Emma Reungoat, Alice Gentil Dit Maurin, Mihayl Varbanov, Julie Blaising, Maud Michelet, Rachel Manuel, Romain Parent, Birke Bartosch, Fabien Zoulim, Florence Ruggiero, Eve-Isabelle Pécheur
The hepatitis C virus (HCV) infects hepatocytes after binding to heparan sulfate proteoglycans, in particular Syndecan-1, followed by recognition of the tetraspanin CD81 and other receptors. Heparan sulfate proteoglycans are found in a specific microenvironment coating the hepatocyte surface called the glycocalyx and are receptors for extracellular matrix proteins, cytokines, growth factors, lipoproteins, and infectious agents. We investigated the mutual influence of HCV infection on the glycocalyx and revealed new links between Syndecan-1 and CD81...
December 8, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27890389/heparanase-confers-a-growth-advantage-to-differentiating-murine-embryonic-stem-cells-and-enhances-oligodendrocyte-formation
#6
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/27866326/the-neuroprotective-peptide-poly-arginine-12-r12-reduces-cell-surface-levels-of-nmda-nr2b-receptor-subunit-in-cortical-neurons-investigation-into-the-involvement-of-endocytic-mechanisms
#7
Gabriella MacDougall, Ryan S Anderton, Adam B Edwards, Neville W Knuckey, Bruno P Meloni
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and reduce calcium influx following in vitro excitotoxicity, as well as reduce brain injury in animal stroke models. Using the neuroprotective peptides poly-arginine R12 (R12) and the NR2B9c peptide fused to the arginine-rich carrier peptide TAT (TAT-NR2B9c; also known as NA-1), we investigated the mechanisms whereby poly-arginine and arginine-rich peptides reduce glutamate-induced excitotoxic calcium influx...
November 20, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27819680/syndecan-1-increases-b-lymphoid-cell-extravasation-in-response-to-hiv-1-tat-via-%C3%AE-v%C3%AE-3-pp60src-pp125fak-pathway
#8
C Urbinati, E Grillo, P Chiodelli, C Tobia, F Caccuri, S Fiorentini, G David, M Rusnati
Syndecan-1 is a heparan sulfate proteoglycan (HSPG) commonly upregulated in AIDS-related B lymphoid malignancies. Tat is the main HIV-1 transactivating factor that has a major role in the pathogenesis of AIDS-related lymphomas (ARL) by engaging heparan sulfate proteoglycans (HSPGs), chemokine receptors and integrins at the lymphoid cell (LC) surface. Here B-lymphoid Namalwa cell clones that do not express or overexpress syndecan-1 (EV-Ncs and SYN-Ncs, respectively) were compared for their responsiveness with Tat: in the absence of syndecan-1, Tat induces a limited EV-Nc migration via C-X-C motif chemokine receptor 4 (CXCR4), G-proteins and Rac...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27811232/mobility-of-hspg-bound-lpl-explains-how-lpl-is-able-to-reach-gpihbp1-on-capillaries
#9
Christopher M Allan, Mikael Larsson, Rachel S Jung, Michael Ploug, André Bensadoun, Anne P Beigneux, Loren G Fong, Stephen G Young
In mice lacking glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1), the LPL secreted by adipocytes and myocytes remains bound to heparan sulfate proteoglycans (HSPGs) on all cells within tissues. That observation raises a perplexing issue: Why isn't the freshly secreted LPL in wild-type mice captured by the same HSPGs, thereby preventing LPL from reaching GPIHBP1 on capillaries? We hypothesized that LPL-HSPG interactions are transient, allowing the LPL to detach and move to GPIHBP1 on capillaries...
January 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/27807067/characterization-of-heparan-sulfate-proteoglycan-positive-recycling-endosomes-isolated-from-glioma-cells
#10
Katarzyna A Podyma-Inoue, Takuya Moriwaki, Anupama R Rajapakshe, Kazue Terasawa, Miki Hara-Yokoyama
BACKGROUND: Heparan sulfate proteoglycans (HSPGs)-dependent endocytic events have been involved in glioma progression. Thus, comprehensive understanding of the intracellular trafficking complexes formed in presence of HSPGs would be important for development of glioma treatments. MATERIALS AND METHODS: Subcellular fractionation was used to separate vesicles containing HSPGs from the rat C6 glioma cell line. Isolated HSPG-positive vesicles were further characterized with liquid chromatography-mass spectrometry...
November 2016: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/27806323/human-sulfatase-1-exerts-anti-tumor-activity-by-inhibiting-the-akt-cdk4-signaling-pathway-in-melanoma
#11
Xiaoli Lou, Bin Sun, Jianxing Song, Yicun Wang, Junhao Jiang, Yang Xu, Zeqiang Ren, Changqing Su
Human sulfatase 1 (hSulf-1) has aryl sulfatase activity. It can reduce the sulfation of cell surface heparan sulfate proteoglycan (HSPG) and inhibit various growth factor receptor-mediated signaling pathways. In most cancers, hSulf-1 is inactivated, which endows cancer cells with increasesed cell proliferation and metastatic activities, inhibition of apoptosis, and decreased sensitivity to radio- and chemotherapy. In this study, we found that hSulf-1 overexpression in melanoma cells can inhibit cell proliferation and induce cell cycle arrest and apoptosis by decreasing the protein kinase B (AKT) phosphorylation and limiting CDK4 nuclear import...
October 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27784961/elucidation-of-the-early-infection-machinery-of-hepatitis-b-virus-by-using-bio-nanocapsule
#12
REVIEW
Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda
Currently, hepatitis B virus (HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan (HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP) via the myristoylated N-terminal sequence of pre-S1 region (from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV...
October 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27693511/infection-of-hepatocytes-with-hcv-increases-cell-surface-levels-of-heparan-sulfate-proteoglycans-uptake-of-cholesterol-and-lipoprotein-and-virus-entry-by-up-regulating-smad6-and-smad7
#13
Fang Zhang, Catherine Sodroski, Helen Cha, Qisheng Li, T Jake Liang
BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor β signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6 and another inhibitory SMAD (SMAD7) promote HCV infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with Japanese fulminant hepatitis-1 (JFH1) HCV cell culture system (HCVcc)...
January 2017: Gastroenterology
https://www.readbyqxmd.com/read/27666777/the-heparanase-heparan-sulfate-proteoglycan-axis-a-potential-new-therapeutic-target-in-sarcomas
#14
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/27644406/rapid-hepatic-clearance-of-full-length-ccn-2-ctgf-a-putative-role-for-lrp1-mediated-endocytosis
#15
K G F Gerritsen, N Bovenschen, T Q Nguyen, D Sprengers, M P Koeners, A N van Koppen, J A Joles, R Goldschmeding, R J Kok
CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min)...
December 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27643669/endothelial-glycocalyx-layer-shedding-following-lung-resection
#16
Alexander Arthur, Phillip J McCall, Lisa Jolly, John Kinsella, Alan Kirk, Ben G Shelley
AIM: We investigated if the serum biomarkers of endothelial glycocalyx layer (EGL) disruption, heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC1) were elevated following lung resection surgery. METHODS: Plasma samples were collected from 16 patients undergoing lobectomy for primary lung cancer. HSPG and SDC1 were measured at five perioperative timepoints. Postoperative oxygenation was recorded. RESULTS: Post-hoc pair wise comparisons showed SDC1 concentration was significantly elevated on postoperative day 2, p < 0...
October 2016: Biomarkers in Medicine
https://www.readbyqxmd.com/read/27589337/impact-of-sulfatase-2-on-cancer-progression-and-prognosis-in-patients-with-renal-cell-carcinoma
#17
Shin Kumagai, Kei Ishibashi, Masao Kataoka, Toshiki Oguro, Yuichirou Kiko, Tomohiko Yanagida, Ken Aikawa, Yoshiyuki Kojima
Heparan sulfate-specific endosulfatase-2 (SULF-2) can modulate the signaling of heparan sulfate proteoglycan-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCC) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCC with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested...
November 2016: Cancer Science
https://www.readbyqxmd.com/read/27580101/tumor-microenvironment-and-angiogenic-blood-vessels-dual-targeting-for-enhanced-anti-glioma-therapy
#18
Quanyin Hu, Ting Kang, Jingxian Feng, Qianqian Zhu, Tianze Jiang, Jianhui Yao, Xinguo Jiang, Jun Chen
Advances in active targeting drug delivery system (DDS) have revolutionized glioma diagnosis and therapy. However, the lack of the sufficient targets on glioma cells and limited penetration capability of DDS have significantly compromised the treatment efficacy. In this study, by taking advantages of the abundant extracellular matrix-derived heparan sulfate proteoglycan (HSPG) and enhanced tumor penetration ability mediated by neuropilin-1 (NRP-1) protein, we reported the ATWLPPR and CGKRK peptide dual-decorated nanoparticulate DDS (designated AC-NP) to achieve angiogenic blood vessels and tumor microenvironment dual-targeting effect...
September 14, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27558418/heparan-sulfate-binding-promotes-accumulation-of-intravitreally-delivered-adeno-associated-viral-vectors-at-the-retina-for-enhanced-transduction-but-weakly-influences-tropism
#19
Kenton T Woodard, Katharine J Liang, William C Bennett, R Jude Samulski
: Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS-independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2...
November 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27545211/hemodynamic-shear-stress-regulates-the-transcriptional-expression-of-heparan-sulfate-proteoglycans-in-human-umbilical-vein-endothelial-cell
#20
J-X Liu, Z-P Yan, Y-Y Zhang, J Wu, X-H Liu, Y Zeng
We have previously demonstrated the adaptive remodeling of endothelial glycocalyx under shear stress. However, the underlying mechanism in glycocalyx remodeling, especially the expression of the components heparan sulfate proteoglycans (HSPGs) under shear stress was not completely known. In the present study, we investigated the expression of those HSPGs (syndecan family and glypican-1) in human umbilical vein endothelial cells (HUVECs) responded to the distinct magnitude of shear stress, and performed a systematic and comprehensive analyze on the relationship between shear stress and HSPGs mRNA expression in a temporal manner...
July 31, 2016: Cellular and Molecular Biology
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