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https://www.readbyqxmd.com/read/28692037/srgn-tgf%C3%AE-2-regulatory-loop-confers-invasion-and-metastasis-in-triple-negative-breast-cancer
#1
Z Zhang, Y Deng, G Zheng, X Jia, Y Xiong, K Luo, Q Qiu, Ni Qiu, J Yin, M Lu, H Liu, Y Gu, Z He
Patients with triple-negative breast cancers (TNBC) are at a high risk for a recurrent or metastatic disease, and the molecular mechanisms associated with this risk are unclear. Proteoglycan serglycin (SRGN) proteins are involved in tumor metastasis, but their role in TNBC has not yet been elucidated. This study investigates the SRGN gene expression and how it regulates TGFβ2 and the downstream signaling of TGFβ2 in TNBC cells and tissues. Our results show that SRGN mRNA and protein expression levels were significantly higher in TNBC cell lines and tumor tissues than that in non-TNBC cells and tissues...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28612914/association-of-serglycin-levels-with-isolated-coronary-artery-ectasia
#2
Harun Kundi, Murat Gok, Canan Topcuoglu, Ender Ornek
BACKGROUND: Serglycin has an important role in the inflammatory status and the relationship between coronary artery ectasia (CAE) and serglycin is still unknown. AIM: In this study, we aimed to investigate association of serglycin level with isolated CAE. METHODS: Fifty-two patients with isolated CAE and 35 individuals with normal coronary angiography were included into the study. Markis classification and number of ectatic coronary arteries were recorded...
June 14, 2017: Kardiologia Polska
https://www.readbyqxmd.com/read/28505124/structure-activity-relationships-of-bioengineered-heparin-heparan-sulfates-produced-in-different-bioreactors
#3
Ha Na Kim, John M Whitelock, Megan S Lord
Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains...
May 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28445977/serglycin-as-a-potential-biomarker-for-glioma-association-of-serglycin-expression-extent-of-mast-cell-recruitment-and-glioblastoma-progression
#4
Ananya Roy, Sanaz Attarha, Holger Weishaupt, Per-Henrik Edqvist, Fredrik J Swartling, Michael Bergqvist, Florian A Siebzehnrubl, Anja Smits, Fredrik Pontén, Elena Tchougounova
Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394734/optimization-of-bioengineered-heparin-heparan-sulfate-production-for-therapeutic-applications
#5
Megan S Lord, MoonSun Jung, John M Whitelock
Heparin has been used clinically as an anti-coagulant for more than 100 y and the major source of this therapeutic is still animal tissues. Contamination issues in some batches of heparin over 10 y ago have highlighted the need to develop alternative methods of production of this essential drug. (1) Bioengineering heparin by expressing serglycin in mammalian cells is a promising approach that was recently reported by the authors. (2) This addendum explores the approaches that the authors are taking to increase the yield of recombinantly expressed serglycin decorated with heparin/heparan sulfate focusing on cell culture and bioreactor conditions and proposes that the cell microenvironment is a key modulator of heparin biosynthesis...
September 3, 2017: Bioengineered
https://www.readbyqxmd.com/read/28193842/experimental-arthritis-is-dependent-on-mouse-mast-cell-protease-5
#6
Richard L Stevens, H Patrick McNeil, Lislaine A Wensing, Kichul Shin, G William Wong, Philip M Hansbro, Steven A Krilis
The constitutive heparin(+) (HP) mast cells (MCs) in mice express mouse MC protease (mMCP)-5 and carboxypeptidase A (mMC-CPA). The amino acid sequence of mMCP-5 is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2(+) MCs in the jejunal mucosa of Trichinella spiralis-infected mice...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28145886/identification-of-novel-follicular-dendritic-cell-sarcoma-markers-fdcsp-and-srgn-by-whole-transcriptome-sequencing
#7
Luisa Lorenzi, Claudia Döring, Tobias Rausch, Vladimir Benes, Silvia Lonardi, Mattia Bugatti, Elias Campo, José Cabeçadas, Ingrid Simonitsch-Klupp, Anita Borges, Jay Mehta, Claudio Agostinelli, Stefano Aldo Pileri, Fabio Facchetti, Martin-Leo Hansmann, Sylvia Hartmann
Follicular dendritic cell (FDC)-sarcoma is a rare neoplasm with morphologic and phenotypic features of FDCs. It shows an extremely heterogeneous morphology, therefore, its diagnosis relys on the phenotype of tumor cells. Aim of the present study was the identification of new specific markers for FDC-sarcoma by whole transcriptome sequencing (WTS). Candidate markers were selected based on gene expression level and biological function. Immunohistochemistry was performed on reactive tonsils, on 22 cases of FDC-sarcomas and 214 control cases including 114 carcinomas, 87 soft tissue tumors, 5 melanomas, 5 thymomas and 3 interdigitating dendritic cell sarcomas...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28115521/platelet-factor-4-binds-to-vascular-proteoglycans-and-controls-both-growth-factor-activities-and-platelet-activation
#8
Megan S Lord, Bill Cheng, Brooke L Farrugia, Simon McCarthy, John M Whitelock
Platelet factor 4 (PF4) is produced by platelets with roles in both inflammation and wound healing. PF4 is stored in platelet α-granules bound to the glycosaminoglycan (GAG) chains of serglycin. This study revealed that platelet serglycin is decorated with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains. Additionally, PF4 had a higher affinity for endothelial-derived perlecan heparan sulfate chains than serglycin GAG chains. The binding of PF4 to perlecan was found to inhibit both FGF2 signaling and platelet activation...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27900574/mast-cell-glycosaminoglycans
#9
REVIEW
B Mulloy, R Lever, C P Page
Mast cells contain granules packed with a mixture of proteins that are released on degranulation. The proteoglycan serglycin carries an array of glycosaminoglycan (GAG) side chains, sometimes heparin, sometimes chondroitin or dermatan sulphate. Tight packing of granule proteins is dependent on the presence of serglycin carrying these GAGs. The GAGs of mast cells were most intensively studied in the 1970s and 1980s, and though something is known about the fine structure of chondroitin sulphate and dermatan sulphate in mast cells, little is understood about the composition of the heparin/heparan sulphate chains...
June 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27819672/serglycin-in-tumor-microenvironment-promotes-non-small-cell-lung-cancer-aggressiveness-in-a-cd44-dependent-manner
#10
J-Y Guo, H-S Hsu, S-W Tyan, F-Y Li, J-Y Shew, W-H Lee, J-Y Chen
Tumor microenvironment (TME) plays an active role in promoting tumor progression. To further understand the communication between TME and tumor cells, this study aimed at investigating the involvement of CD44, a type I cell surface receptor, in the crosstalk between tumor cells and TME. We have previously shown that chondroitin sulfate proteoglycan serglycin (SRGN), a CD44-interacting factor, was preferentially secreted by cancer-associated fibroblasts (CAFs) for promoting tumor growth in breast cancer patients...
April 27, 2017: Oncogene
https://www.readbyqxmd.com/read/27809309/extracellular-serglycin-upregulates-the-cd44-receptor-in-an-autocrine-manner-to-maintain-self-renewal-in-nasopharyngeal-carcinoma-cells-by-reciprocally-activating-the-mapk-%C3%AE-catenin-axis
#11
Qiaoqiao Chu, Hongbing Huang, Tiejun Huang, Li Cao, Lixia Peng, Simei Shi, Lisheng Zheng, Liang Xu, Shijun Zhang, Jialing Huang, Xinjian Li, Chaonan Qian, Bijun Huang
Serglycin is a proteoglycan that was first found to be secreted by hematopoietic cells. As an extracellular matrix (ECM) component, serglycin promotes nasopharyngeal carcinoma (NPC) metastasis and serves as an independent, unfavorable NPC prognostic indicator. The detailed mechanism underlying the roles of serglycin in cancer progression remains to be clarified. Here, we report that serglycin knockdown in NPC cells inhibited cell sphere formation and tumor seeding abilities. Serglycin downregulation enhanced high-metastasis NPC cell sensitivity to chemotherapy...
November 3, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27445159/bioengineered-human-heparin-with-anticoagulant-activity
#12
Megan S Lord, Bill Cheng, Fengying Tang, J Guy Lyons, Jelena Rnjak-Kovacina, John M Whitelock
Heparin is a carbohydrate anticoagulant used clinically to prevent thrombosis, however impurities can limit its efficacy. Here we report the biosynthesis of heparin-like heparan sulfate via the recombinant expression of human serglycin in human cells. The expressed serglycin was also decorated with chondroitin/dermatan sulfate chains and the relative abundance of these glycosaminoglycan chains changed under different concentrations of glucose in the culture medium. The recombinantly expressed serglycin produced with 25mM glucose present in the culture medium was found to possess anticoagulant activity one-seventh of that of porcine unfractionated heparin, demonstrating that bioengineered human heparin-like heparan sulfate may be a safe next-generation pharmaceutical heparin...
November 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27267469/serglycin-proteoglycans-limit-enteropathy-in-trichinella-spiralis-infected-mice
#13
Ananya Roy, Osama Sawesi, Ulrika Pettersson, Anders Dagälv, Lena Kjellén, Anna Lundén, Magnus Åbrink
BACKGROUND: Serglycin proteoglycans are essential for maturation of secretory granules and for the correct granular storage of cationic proteases in hematopoietic cells, e.g. mast cells. However, little is known about the in vivo functions of serglycin proteoglycans during infection. Here we investigated the potential role of serglycin proteoglycans in host defense after infection with the nematode Trichinella spiralis. RESULTS: Twelve days post infection lack of serglycin proteoglycans caused significantly increased enteropathy...
June 8, 2016: BMC Immunology
https://www.readbyqxmd.com/read/27223472/targeting-serglycin-prevents-metastasis-in-murine-mammary-carcinoma
#14
Ananya Roy, Julia Femel, Elisabeth J M Huijbers, Dorothe Spillmann, Erik Larsson, Maria Ringvall, Anna-Karin Olsson, Magnus Åbrink
In hematopoietic cells, serglycin proteoglycans mainly contribute to proper storage and secretion of inflammatory mediators via their negatively charged glycosaminoglycans. Serglycin proteoglycans are also expressed in cancer cells where increased expression has been linked to poor prognosis. However, the serglycin-dependent mediators promoting cancer progression remain to be determined. In the present study we report that genetic ablation of serglycin proteoglycan completely blocks lung metastasis in the MMTV-PyMT-driven mouse breast cancer model, while serglycin-deficiency did not affect primary tumour growth or number of mammary tumours...
2016: PloS One
https://www.readbyqxmd.com/read/27179695/estrogen-receptor-beta-modulates-breast-cancer-cells-functional-properties-signaling-and-expression-of-matrix-molecules
#15
Zoi Piperigkou, Panagiotis Bouris, Maurizio Onisto, Marco Franchi, Dimitris Kletsas, Achilleas D Theocharis, Nikos K Karamanos
Estrogen receptors have pivotal roles in breast cancer growth and progression. ERα has been clearly shown to play key role in hormone-dependent breast cancer properties, but little is known for the isoform ERβ. To evaluate the role of ERβ, we established stably transfected ERβ-suppressed MDA-MB-231 breast cancer cells by knocking down the human ERβ gene, using specific shRNA lentiviral particles. As observed by scanning electron microscopy, the ERβ suppression induces significant phenotypic changes in these cells, as compared to the control cells...
December 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27042303/il-6-and-il-17a-degradation-by-mast-cells-is-mediated-by-a-serglycin-serine-protease-axis
#16
Ida Waern, Iulia Karlsson, Gunnar Pejler, Sara Wernersson
Mast cells contain large amounts of fully active proteases that are stored in complex with serglycin proteoglycan in their secretory granules. Upon degranulation, such serglycin:protease complexes are released to the extracellular space and can potentially have an impact on the local inflammatory reaction, either through direct effects of serglycin proteoglycan or through effects mediated by its bound proteases. The objective of this study was to address this scenario by investigating the possibility that serglycin-associated proteases can regulate levels of pro-inflammatory cytokines...
March 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/26756195/serglycin-determines-secretory-granule-repertoire-and-regulates-natural-killer-cell-and-cytotoxic-t-lymphocyte-cytotoxicity
#17
Vivien R Sutton, Amelia J Brennan, Sarah Ellis, Jill Danne, Kevin Thia, Misty R Jenkins, Ilia Voskoboinik, Gunnar Pejler, Ricky W Johnstone, Daniel M Andrews, Joseph A Trapani
The anionic proteoglycan serglycin is a major constituent of secretory granules in cytotoxic T lymphocyte (CTL)/natural killer (NK) cells, and is proposed to promote the safe storage of the mostly cationic granule toxins, granzymes and perforin. Despite the extensive defects of mast cell function reported in serglycin gene-disrupted mice, no comprehensive study of physiologically relevant CTL/NK cell populations has been reported. We show that the cytotoxicity of serglycin-deficient CTL and NK cells is severely compromised but can be partly compensated in both cell types when they become activated...
March 2016: FEBS Journal
https://www.readbyqxmd.com/read/26755884/proteoglycans-in-liver-cancer
#18
REVIEW
Kornélia Baghy, Péter Tátrai, Eszter Regős, Ilona Kovalszky
Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types...
January 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/26694746/serglycin-in-quiescent-and-proliferating-primary-endothelial-cells
#19
Trine M Reine, Tram T Vuong, Arkady Rutkovskiy, Astri J Meen, Jarle Vaage, Trond G Jenssen, Svein O Kolset
Proteoglycans are fundamental components of the endothelial barrier, but the functions of the proteoglycan serglycin in endothelium are less described. Our aim was to describe the roles of serglycin in processes relevant for endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVEC) were cultured in vitro and the expression of proteoglycans was investigated. Dense cell cultures representing the quiescent endothelium coating the vasculature was compared to sparse activated cell cultures, relevant for diabetes, cancer and cardiovascular disease...
2015: PloS One
https://www.readbyqxmd.com/read/26692491/intestinal-and-peritoneal-mast-cells-differ-in-kinetics-of-quantal-release
#20
COMPARATIVE STUDY
Santiago Balseiro-Gomez, M Pilar Ramirez-Ponce, Jorge Acosta, Eva Ales, Juan A Flores
5-hydroxytriptamine (5-HT, serotonin) storage and release in mast cell (MC) secretory granules (SG) are dependent on serglycin proteoglycans (PG). This notion is based on the studies of MC of the connective tissue subtype that predominantly contain PG of the heparin type, whereas intestinal mucosal MC, which contain predominantly chondroitin sulfate, have been poorly explored. In the present study, we addressed the possibility that PG contents may differently affect the storage and release of preformed mediators in these two MC subclasses and explain in part their different functional properties...
January 15, 2016: Biochemical and Biophysical Research Communications
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