scholarly journals Heparan Sulfate Proteoglycans May Promote or Inhibit Cancer Progression by Interacting with Integrins and Affecting Cell Migration

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Mariana A. Soares ◽  
Felipe C. O. B. Teixeira ◽  
Miguel Fontes ◽  
Ana Lúcia Arêas ◽  
Marcelo G. Leal ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Cancer Progression ◽  
Heparan Sulfate Proteoglycans ◽  
Transmembrane Receptors ◽  
Surface Molecules ◽  
Cell Matrix ◽  
Cell Organization ◽  
The Relationship

The metastatic disease is one of the main consequences of tumor progression, being responsible for most cancer-related deaths worldwide. This review intends to present and discuss data on the relationship between integrins and heparan sulfate proteoglycans in health and cancer progression. Integrins are a family of cell surface transmembrane receptors, responsible for cell-matrix and cell-cell adhesion. Integrins’ main functions include cell adhesion, migration, and survival. Heparan sulfate proteoglycans (HSPGs) are cell surface molecules that play important roles as cell receptors, cofactors, and overall direct or indirect contributors to cell organization. Both molecules can act in conjunction to modulate cell behavior and affect malignancy. In this review, we will discuss the different contexts in which various integrins, such asα5,αV,β1, andβ3, interact with HSPGs species, such as syndecans and perlecans, affecting tissue homeostasis.

scholarly journals Heparanase Facilitates Cell Adhesion and Spreading by Clustering of Cell Surface Heparan Sulfate Proteoglycans

PLoS ONE ◽  
2008 ◽  
Vol 3 (6) ◽  
pp. e2319 ◽  
Author(s):  
Flonia Levy-Adam ◽  
Sari Feld ◽  
Edith Suss-Toby ◽  
Israel Vlodavsky ◽  
Neta Ilan
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans

scholarly journals Protein kinase C regulates the recruitment of syndecan-4 into focal contacts.

1995 ◽  
Vol 6 (11) ◽  
pp. 1503-1513 ◽  
Author(s):  
P C Baciu ◽  
P F Goetinck
Keyword(s):  
Protein Kinase C ◽  
Cell Adhesion ◽  
Protein Kinase ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Matrix Deposition ◽  
Kinase C ◽  
Focal Contacts ◽  
The Matrix ◽  
Migratory Cells

Cell surface heparan sulfate proteoglycans have been implicated as co-receptors facilitating cell adhesion and growth factor binding. Recent studies on the role of a family of transmembrane heparan sulfate proteoglycans, syndecans, in cell adhesion has identified one member, syndecan-4, to be present within focal contacts. The current study investigates the mechanisms regulating the association of syndecan-4 with focal contacts based upon its immunolocalization with vinculin in quiescent, serum-stimulated, and 12-0-tetradecanoylphorbol 13-acetate (TPA)-induced cultures. In quiescent cells, syndecan-4 did not localize to focal contacts. However, activation of protein kinase C by TPA or serum induces the active recruitment of syndecan-4 into focal contacts. This induction preferentially localizes syndecan-4 to focal contacts behind the leading lamella, the subnuclear region, and along the trailing edge of migratory cells. Focal contacts in either freshly adhered cells or in the leading lamellae of migrating cells did not stain for syndecan-4. In addition to the observed subcellular distribution and recruitment, syndecan-4 was observed to co-localize with endogenously synthesized fibronectin fibrils within focal contacts as well as with fibrils present in the matrix. These findings suggest that protein kinase C activation results in syndecan-4 recruitment to focal contacts and its association with sites of matrix deposition.

scholarly journals Distinct glycosaminoglycan chain length and sulfation patterns required for cellular uptake of Tau, Aβ, and α-Synuclein

2017 ◽  
Author(s):  
Barbara E. Stopschinski ◽  
Brandon B. Holmes ◽  
Gregory M. Miller ◽  
Jaime Vaquer-Alicea ◽  
Linda C. Hsieh-Wilson ◽  
...  
Keyword(s):  
Cell Surface ◽  
Neurodegenerative Diseases ◽  
Heparan Sulfate ◽  
Chain Length ◽  
Cellular Uptake ◽  
Genetic Manipulation ◽  
Heparan Sulfate Proteoglycans ◽  
Cell Uptake ◽  
Major Genes

AbstractTranscellular propagation of aggregate “seeds” has been proposed to mediate progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We have previously determined that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface. This mediates uptake and intracellular seeding. The specificity and mode of binding to HSPGs has been unknown. We used modified heparins to determine the size and sulfation requirements of glycosaminoglycan (GAGs) binding to aggregates in biochemical and cell uptake and seeding assays. Aggregates of tau require a precise GAG architecture with defined sulfate moieties in the N- and 6-O-positions, whereas α-synuclein and Aβ rely slightly more on overall charge on the GAGs. To determine the genetic requirements for aggregate uptake, we individually knocked out the major genes of the HSPG synthesis pathway using CRISPR/Cas9 in HEK293T cells. Knockout of EXT1, EXT2 and EXTL3, N-sulfotransferase (NDST1), and 6-O-sulfotransferase (HS6ST2) significantly reduced tau uptake. α-Synuclein was not sensitive to HS6ST2 knockout. Good correlation between pharmacologic and genetic manipulation of GAG binding by tau and α-synuclein indicates specificity that may help elucidate a path to mechanism-based inhibition of transcellular propagation of pathology.

BETA2/NeuroD Protein Transduction Requires Cell Surface Heparan Sulfate Proteoglycans

2006 ◽  
Vol 0 (0) ◽  
pp. 061206073830001
Author(s):  
Hirofumi Noguchi ◽  
Michiko Ueda ◽  
Shinichi Matsumoto ◽  
Naoya Kobayashi ◽  
Shuji Hayashi
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Protein Transduction

scholarly journals Interaction of an Outer Membrane Protein of Enterotoxigenic Escherichia coli with Cell Surface Heparan Sulfate Proteoglycans

2002 ◽  
Vol 70 (3) ◽  
pp. 1530-1537 ◽  
Author(s):  
James M. Fleckenstein ◽  
James T. Holland ◽  
David L. Hasty
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Eukaryotic Cells ◽  
Heparin Binding ◽  
Wild Type ◽  
E Coli

ABSTRACT We have previously shown that enterotoxigenic invasion protein A (Tia), a 25-kDa outer membrane protein encoded on an apparent pathogenicity island of enterotoxigenic Escherichia coli (ETEC) strain H10407, mediates attachment to and invasion into cultured human gastrointestinal epithelial cells. The epithelial cell receptor(s) for Tia has not been identified. Here we show that Tia interacts with cell surface heparan sulfate proteoglycans. Recombinant E. coli expressing Tia mediated invasion into wild-type epithelial cell lines but not invasion into proteoglycan-deficient cells. Furthermore, wild-type eukaryotic cells, but not proteoglycan-deficient eukaryotic cells, attached to immobilized polyhistidine-tagged recombinant Tia (rTia). Binding of epithelial cells to immobilized rTia was inhibited by exogenous heparan sulfate glycosaminoglycans but not by hyaluronic acid, dermatan sulfate, or chondroitin sulfate. Similarly, pretreatment of eukaryotic cells with heparinase I, but not pretreatment of eukaryotic cells with chrondroitinase ABC, inhibited attachment to rTia. In addition, we also observed heparin binding to both immobilized rTia and recombinant E. coli expressing Tia. Heparin binding was inhibited by a synthetic peptide representing a surface loop of Tia, as well as by antibodies directed against this peptide. Additional studies indicated that Tia, as a prokaryotic heparin binding protein, may also interact via sulfated proteoglycan molecular bridges with a number of mammalian heparan sulfate binding proteins. These findings suggest that the binding of Tia to host epithelial cells is mediated at least in part through heparan sulfate proteoglycans and that ETEC belongs on the growing list of pathogens that utilize these ubiquitous cell surface molecules as receptors.

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