• gene
  • They consist of four members: syndecan-1, syndecan-2 (fibroglycan), syndecan-3(N-syndecan), and syndecan-4 (amphiglycan/ryudocan) each encoded by a distinct gene (Teng et al. (springer.com)
  • We review here the input of gene expression profiling of myeloma cells and of their tumor microenvironment to develop new tumor classifiers, to better understand the biology of myeloma cells, to identify some mechanisms of drug sensitivity and resistance, to identify new myeloma growth factors, and to depict the complex interactions between tumor cells and their microenvironment. (aacrjournals.org)
  • For example, gene expression profile (GEP) analysis of primary myeloma cells from 92 patients was analyzed according to their immunoglobulin types and light chain subtypes, revealing that several clusters of genes involved in various biological functions could significantly discriminate those different types of myeloma ( 20 ). (aacrjournals.org)
  • Pleiotrophin (PTN) also known as heparin-binding brain mitogen (HBBM) or heparin-binding growth factor 8 (HBGF-8) or neurite growth-promoting factor 1 (NEGF1) or heparin affinity regulatory peptide (HARP) or heparin binding growth associated molecule (HB-GAM) is a protein that in humans is encoded by the PTN gene. (wikipedia.org)
  • Syndecan-2 is a protein that in humans is encoded by the SDC2 gene. (wikipedia.org)
  • The envelope glycoprotein structure consists of two protein subunits cleaved from a Gp160 protein precursor encoded for by the HIV-1 env gene: the Gp120 external subunit, and the Gp41 transmembrane subunit. (wikipedia.org)
  • Syndecan-3, also called SYND3 is a protein that in humans is encoded by the SDC3 gene. (bosterbio.com)
  • Furthermore, mice ablated for the syndecan-1 or -4 gene do not show major developmental abnormalities, but they do show striking pathological phenotypes when challenged with infectious or inflammatory stimuli and conditions, suggesting that certain functions of syndecans are specific and cannot be compensated for by other syndecans or other HSPGs. (readbyqxmd.com)
  • Syndecan 1 is a protein which in humans is encoded by the SDC1 gene. (wikipedia.org)
  • Following co-culture experiments and the determination that MK was one of the factors that was conferring chemo-resistance to the wild, non-resistant cell type, the gene for MK was transfected into WT cells to determine if MK was overexpressed in the WT cells themselves, would the cells become resistant to chemotherapy independent of resistant cell influence. (wikipedia.org)
  • Syndecans 1 and 3 and syndecans 2 and 4, making up separate subfamilies, arose by gene duplication and divergent evolution from a single ancestral gene. (wikipedia.org)
  • Thrombospondin 1, abbreviated as THBS1, is a protein that in humans is encoded by the THBS1 gene. (wikipedia.org)
  • Sulfatase 1, also known as SULF1, is an enzyme which in humans is encoded by the SULF1 gene. (wikipedia.org)
  • HSPGs
  • Here we report on the nature of HSPGs inducibly expressed on the surface of macrophages that confer these cells with the capacity to regulate endogenous growth factor activity. (ox.ac.uk)
  • The major cell membrane HSPGs are the transmembrane syndecans and the glycosylphosphatidylinositol (GPI) anchored glypicans. (wikipedia.org)
  • Tau fibrils bind to cell surface HSPGs in a similar manner to prions, triggering intracellular fibril aggregation, suggesting a unifying mechanism for tauopathies and synucleopathies, and potential drug targets. (wikipedia.org)
  • The function of HSPGs extends beyond providing an extracellular matrix (ECM) structure and scaffold for cells. (wikipedia.org)
  • membrane
  • hLin-7b associates with the channel as a part of a multimeric complex on the basolateral membrane similar to a basolateral membrane complex in C. elegans vulva progenitor cells. (physiology.org)
  • In these cells, the asymmetric expression of weakly inward-rectifying K + channels on the apical membrane and more strongly rectifying K + channels on the basolateral membrane may increase the fidelity of the secretory process, ensuring that potassium preferentially exits the cell across the apical membrane into the tubule lumen in concert with the demands of potassium homeostasis ( 10 ). (physiology.org)
  • The formation of this complex stimulates the release of a fusogenic peptide inducing the fusion of the viral membrane with the membrane of the target host cell. (wikipedia.org)
  • Laminins are basement membrane components thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. (wikipedia.org)
  • In contrast to lysosomal active sulfatases, QSulf1 localizes exclusively to the cell surface by interacting hydrophilically with a non-heparan sulfate outer membrane component, and is enzymatically active at a neutral pH. (wikipedia.org)
  • Therefore, unlike syndecans the heparan sulfate glycosaminoglycan chains attached to glypicans are located rather close to the cell-membrane. (wikipedia.org)
  • integrin
  • While P- and L-selectin facilitation of cellular contacts during hematogenous metastasis is being accepted as a potential target of heparin, here we propose that heparin may also interfere with integrin activity and thereby affect cancer progression. (hindawi.com)
  • In addition to direct targeting of selectin and integrins, recent evidence suggests that heparin possesses selectin (P- and L-selectin) and also integrin inhibitory activity [ 7 - 9 ]. (hindawi.com)
  • a) Schematic presentation of selectin- and integrin-mediated cancer cell interactions with several blood constituents (e.g., platelets, leukocytes, and endothelial cells) during hematogenous metastasis. (hindawi.com)
  • When OPN is associated with syndecan-4, syndecan-4 masks both the thrombin cleavage and the integrin binding sites within OPN. (rupress.org)
  • Syndecan-4, when bound to OPN, masks not only thrombin cleavage but also integrin binding sites within OPN molecules, thus regulating various OPN functions. (rupress.org)
  • Integrin-mediated mechanotransduction in vascular smooth muscle cells (VSMCs) plays an important role in the physiological control of tissue blood flow and vascular resistance. (physiology.org)
  • ectodomain
  • Aim 2 will elucidate the structural features of syndecan-1 ectodomain HS that promote S. aureus keratitis, and Aim 3 will determine the biological mechanism of how syndecan-1 ectodomains inhibit S. aureus killing by neutrophils. (grantome.com)
  • All syndecans have an N-terminal signal peptide, an ectodomain, a single hydrophobic transmembrane domain, and a short C-terminal cytoplasmic domain. (wikipedia.org)
  • The most obvious differences between syndecans include (together with differences in distribution) the subclassification of the family depending on the existence of GAG binding sites either at both ends of the ectodomain (syndecan-1 and - 3) or at the distal part only (syndecan-2 and -4) and a relatively long Thr-Ser-Pro-rich area in the middle of syndecan- 3's ectodomain. (wikipedia.org)
  • Tumor
  • This review summarizes recent findings about potential mechanisms of tumor cell interactions in the vasculature and antimetastatic activities of heparin. (hindawi.com)
  • Metastasis is facilitated by cell-cell interactions between tumor cells and the endothelium in distant tissues. (hindawi.com)
  • Hematogenous cancer metastasis is a multistep cascade encompassing process, starting with local invasion of tumor cells at primary tumors, survival in systemic circulation, extravasation in secondary sites, and ending with establishment of growing metastatic lesions. (hindawi.com)
  • The metastatic capacity of tumor cells correlates with their ability to exit from the blood circulation, to colonize distant organs, and to grow in distant organs [ 1 ]. (hindawi.com)
  • The organ-specific character of metastasis has been already observed by S. Paget more than a century ago, and the "seed and soil" hypothesis postulates specific interactions of tumor cells with the "friendly" environment of distant organs that enables the establishment of metastasis and subsequent growth [ 2 ]. (hindawi.com)
  • However, although IL-6 is essential, it is not sufficient and additional factors, produced by the microenvironment or the tumor cells themselves, are required together with IL-6 to promote tumor growth ( 3 ). (aacrjournals.org)
  • Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis. (wikipedia.org)
  • Altered syndecan-2 expression has been detected in several different tumor types. (wikipedia.org)
  • HGF is overexpressed by multiple myeloma cells, which aids tumor angiogenesis, cell migration, and cell survival. (pubmedcentralcanada.ca)
  • However, little is known about how this process is regulated in tumor cells. (pubmedcentralcanada.ca)
  • The TSP-1 3TSR (a recombinant version of the THBS1 antiangiogenic domain containing all three thrombosopondin-1 type 1 repeats) can activate transforming growth factor beta 1 (TGFβ1) and inhibit endothelial cell migration, angiogenesis, and tumor growth. (wikipedia.org)
  • bind
  • It is unknown whether HBDs within OPN really bind to heparin and HS. (rupress.org)
  • Importantly, proper glycosylation is necessary to localize to the cell surface, possibly to bind HS moieties, and was required for enzymatic activity. (wikipedia.org)
  • migration
  • The N-terminal heparin-binding domain of TSP1, when isolated as a 25kDa fragment, has been shown to be a potent inducer of cell migration at high concentrations. (wikipedia.org)
  • However, when the heparin-binding domain of TSP1 is cleaved, the remaining anti-angiogenic domains have been shown to have decreased anti-angiogenic activity at low concentrations where increased endothelial cell (EC) migration occurs. (wikipedia.org)
  • heparanase
  • Effects of small interfering RNA targeting heparanase-1 combined with heparin on invasiveness of mouse hepatocellular carcinoma cell lines. (biomedsearch.com)
  • BACKGROUND AND OBJECTIVE: Heparanase-1 (HPA-1) can promote angiogenesis and metastasis of malignant tumors and plays an important role in the genesis and development of tumors. (biomedsearch.com)
  • In this Paper of the Week, Vishnu Ramani and colleagues find that heparanase, which cleaves heparan sulfate chains, is responsible for enhancing HGF expression in myeloma cells. (pubmedcentralcanada.ca)
  • Interestingly, although heparanase enzyme activity was required for the shedding of syndecan-1 from the cell surface, enzymatic activity was not required for HGF up-regulation. (pubmedcentralcanada.ca)
  • This suggests that heparanase contains two different functional domains, each of which contributes to myeloma cell survival by stimulating the two components of the HGF/syndecan-1 signaling complex. (pubmedcentralcanada.ca)
  • Immunohistochemical staining shows greatly increased levels of HGF ( brown ) in tumors formed in SCID mice from myeloma cells containing high levels of heparanase expression. (pubmedcentralcanada.ca)
  • Heparanase partially or completely cleaves heparan sulfate to expose a binding site in the N-terminal 50 amino acids of syndecan-1. (wikipedia.org)
  • differentiation
  • Lymphocytes express and lose syndecan at specific stages of differentiation. (springer.com)
  • In this study we have investigated a possible role of RAGE and amphoterin in the retinoic acid-induced differentiation of neuroblastoma cells. (jove.com)
  • transmembrane
  • there must be reciprocal action (synergy, intercommunication) between gp120 and the CCR5 transmembrane domains CCR5 is essential for the spread of the R5-strain of the HIV-1 virus. (wikipedia.org)
  • The transmembrane domains contain an unusual alanine/glycine sequence motif, while the cytoplasmic domain is essentially composed of two regions of conserved amino acid sequence (C1 and C2), separated by a central variable sequence of amino acids that is distinct for each family member (V). In mammalian cells, syndecans are expressed by unique genes located on different chromosomes. (wikipedia.org)
  • molecular weight
  • Heparin and low-molecular-weight (LMW) heparin are commonly used anticoagulants for treatment of cancer-associated thromboembolism in cancer patients [ 10 , 11 ]. (hindawi.com)
  • Syndecan-4 is one of the four vertebrate syndecans and has a molecular weight of ~20 kDa. (wikipedia.org)
  • Midkine is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin (NEGF1, 46% homologous with MK). (wikipedia.org)
  • mediates
  • Knowledge of the mechanism by which this strain of HIV-1 mediates infection has prompted research into the development of therapeutic interventions to block CCR5 function. (wikipedia.org)
  • correlates
  • The degree of oligomerization correlates with the activity of kinases, so the degree of clustering of syndecan-4 correlates to PKC activity. (wikipedia.org)
  • growth
  • Myeloma cells are strongly dependent on their microenvironment, which produces cell communication signals, in particular myeloma growth factors. (aacrjournals.org)
  • sites that are not favored growth places for MM cells. (myeloma-europe.org)
  • A reasonable explanation for this tropism is that MM cells are critically dependent on factors that are present only within the human bone marrow, for their prolonged survival and growth. (myeloma-europe.org)
  • Possible candidates for factors that sustain the growth of MM cells in the bone marrow include glycoproteins in the extracellular matrix (e.g. fibronec-tin, thrombospondin-1, osteopontin) or cytokines secreted by cells in the marrow microenvironment. (myeloma-europe.org)
  • Monocyte/macrophages play important roles in regulating tissue growth and angiogenesis through the controlled release of heparin-binding growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor, and heparin binding epidermal growth factor. (ox.ac.uk)
  • Pleiotrophin is an 18-kDa growth factor that has a high affinity for heparin. (wikipedia.org)
  • Syndecan-4 interacts with extracellular matrix, anticoagulants, and growth-factors. (wikipedia.org)
  • Syndecan-4 is also a regulator of fibroblast growth factor-2 (FGF-2) signaling. (wikipedia.org)
  • Because the tight correlation between syndecan-4 and growth factors, the efficiency of angiogenic therapies have been thought to relate to syndecan-4. (wikipedia.org)
  • Growth factor signaling may be disrupted by changes in syndecan-4 expression. (wikipedia.org)
  • Syndecan-1 is a sponge for growth factors, with binding largely via heparan sulfate chains. (wikipedia.org)
  • endothelial cell
  • Laminar shear stress (LS) promotes endothelial cell (EC) quiescence, whereas oscillatory shear stress (OS) promotes EC turnover and dysfunction, which could lead to pathological angiogenesis. (ahajournals.org)
  • The successful penetration of the endothelial cell layer that lines the interior surface of blood vessels is an important process in the formation of blood borne tumour metastases. (wikipedia.org)
  • mediate
  • This may be explained in part by the ability of the heparin-binding domain to mediate attachment of TSP1 to cells, allowing the other domains to exert their effects. (wikipedia.org)
  • mechanism
  • However, the molecular mechanism by which syndecan-4 regulates complex host defense responses remains to be elucidated. (rupress.org)
  • mechanotransduction in vascular smooth muscle cells (VSMCs) is a fundamental mechanism underlying the vascular myogenic response ( 9 ), in which vascular smooth muscle contracts in response to increased intralumenal pressure or relaxes in response to decreased pressure ( 11 , 21 ). (physiology.org)
  • 1 This VSMC behavior is a key mechanism for the establishment of vascular tone and the autoregulation of blood flow ( 8 ). (physiology.org)
  • May have a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism (By similarity). (bosterbio.com)
  • In addition, the mechanism for such anti-apoptotic (anti-cell death) activity was studied, specifically using the chemotherapeutic Doxorubicin (Adriamycin) on osteosarcoma (Saos2) cells. (wikipedia.org)
  • integrins
  • The RGD sequence (Arg-Gly-Asp) is located in III10 and is the site of cell attachment via α5β1 and αVβ3 integrins on the cell surface. (wikipedia.org)
  • Function-blocking antibodies to α 5 β 1 - and α v β 3 -integrins also blocked the micromechanical cell event in a concentration-dependent manner. (physiology.org)
  • Arising from their complex function in mediating cell attachment and signal transduction, integrins have been more widely recognized to be important for cellular mechanotransduction. (physiology.org)
  • angiogenesis
  • The separate roles that the heparin-binding region of TSP1 plays at high versus low concentrations may be in part responsible for regulating the two-faced nature of TSP1 and giving it a reputation of being both a positive and negative regulator of angiogenesis. (wikipedia.org)
  • novel
  • Juuti A, Nordling S, Lundin J, Louhimo J, Haglund C. Syndecan-1 expression - a novel prognostic marker in pancreatic cancer. (springer.com)
  • The proposed studies will use both novel and established genetic, biochemical, and cell biological approaches in conjunction with in vivo models of bacterial keratitis. (grantome.com)
  • Thus, syndecan-4 is a critical intrinsic regulator of inflammatory reactions via its effects on OPN function and is a potential novel therapeutic tool for treating inflammatory diseases. (rupress.org)
  • inhibit
  • Publications] Yamagishi, S.: 'Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells'Diabetologia. (nii.ac.jp)
  • Thus, glycosides inhibit glycoconjugate formation and provide a tool for studying glycan function in cells and whole organisms. (go.jp)
  • This indicates that MK caused the cells to initiate the survival pathway (via PKB, mTOR, and Bad activation) and inhibit the senescent or apoptotic pathway (via inhibiting caspase-3) encouraging the chemoresistance seen in resistant cells and in the co-culture experiments. (wikipedia.org)
  • focal adhesions
  • Step increases of an upward ( z -axis) pulling force (800∼1,600 pN) applied to the bead-cell contact site for FN-specific focal adhesions induced a myogenic-like, force-generating response from the VSMC, resulting in a counteracting downward pull by the cell. (physiology.org)
  • Syndecan-4 has more widespread distribution than other syndecans and it is the only syndecan that has been found consistently in focal adhesions. (wikipedia.org)
  • bFGF
  • Of these, one of the most extensively studied is the interaction between heparin and FGF2 (bFGF). (sigmaaldrich.com)
  • Furthermore, HGF and VEGF produced by myeloma cells, as well as bFGF produced by the microenvironment, are potent angiogenic cytokines. (myeloma-europe.org)
  • Mice
  • Publications] Takamura, T,: 'Transgenic mice overexpressing type 2 nitric oxide synthase in pancreatic β cells develop insulin-dependent diabetes without insulitis'J. (nii.ac.jp)
  • Preliminary studies showed that mice deficient in syndecan-1 significantly resist corneal infection by Staphylococcus aureus, suggesting that syndecan-1 is an important host factor that promotes S. aureus keratitis. (grantome.com)
  • Furthermore, human MM cells usually do not grow in immuno-compromised mice, but are able to grow inside human bone fragments implanted. (myeloma-europe.org)
  • Importantly, syndecan-4-deficient (Syn4KO) mice are more susceptible to hepatic injury, and the thrombin-cleaved form of OPN is significantly elevated in Syn4KO mice as compared with wild-type mice after ConA injection. (rupress.org)
  • Finally, we demonstrate that administration of purified syndecan-4 protects mice from ConA-induced hepatic injury. (rupress.org)
  • Importantly, administration of exogenous syndecan-4 protects mice from ConA-induced hepatic injury. (rupress.org)
  • Acute Brain Trauma in Mice Followed By Longitudinal Two-photon Imaging Mikhail Paveliev 1 , Mikhail Kislin 1 , Dmitry Molotkov 1 , Mikhail Yuryev 1 , Heikki Rauvala 1 , Leonard Khiroug 1 1 Neuroscience Center, University of Helsinki Acute brain trauma is a severe injury that has no adequate treatment to date. (jove.com)
  • fibroglycan
  • David G, Bai XM, Van der Schueren B, Marynen P, Cassiman JJ, Van den Berghe H. Spatial and temporal changes in the expression of fibroglycan (syndecan-2) during mouse embryonic development. (springer.com)
  • cytokine
  • Osteopontin (OPN) is a T helper type 1 immunoregulatory cytokine that plays a critical role in various inflammatory disorders. (rupress.org)
  • SDC3
  • Rabbit IgG polyclonal antibody for Syndecan-3(SDC3) detection. (bosterbio.com)
  • A synthetic peptide corresponding to a sequence at the N-terminus of mouse Syndecan 3/SDC3 (45-60aa AQRWRNENFERPVDLE), identical to the related rat sequence, and different from the related human sequence by one amino acid. (bosterbio.com)
  • biosynthesis
  • From this and early work on the fundamental stages of HS/heparin biosynthesis using a mouse mastocytoma cell free system a lot is known about the order of enzyme reactions and specificity. (wikipedia.org)
  • biological
  • Heparin contains several biological activities that may affect several steps in metastatic cascade. (hindawi.com)
  • ID NO:. 2 ranging between a fragment represented by Gln23Gly50 to a fragment represented by Gln23-Gln210, and a heparan sulfate glycosaminoglycan chain covalently linked thereto which syndecan is isolated free of any biological macromolecules which are present in a natural source of the proteolglycan. (google.es)