Functions of Cell Surface Heparan Sulfate Proteoglycans

Bernfield, Merton; Götte, Martin; Park, Pyong Woo; Reizes, Ofer; Fitzgerald, Marilyn L.; Lincecum, John; Zako, Masaru

doi:10.1146/annurev.biochem.68.1.729

Cited by 2,487 publications

(2,619 citation statements)

References 261 publications

Supporting

Mentioning

2,555

Contrasting

Unclassified

Order By: Relevance

“…The function of syndecan-1 has been largely described in normal and tumor epithelial cells where it plays major roles, partly due to its ability to bind growth factors and chemokines (Bernfield et al, 1999;Sanderson et al, 2004). On MMC, the function of syndecan-1 is not fully elucidated yet.…”

Section: Discussionmentioning

confidence: 99%

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

et al. 2006

View full text Add to dashboard Cite

The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro.To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed their expression and biological activity. Comparing Affymetrix DNA-microarray-expression-profiles of CD138-purified plasma-cells from 65 MM-patients and 7 normal individuals to those of plasmablasts and B-cells, we found 5/10 EGF-family genes to be expressed in MMC. Neuregulin-2 and neuregulin-3 were expressed by MMC only, while neuregulin-1, amphiregulin and transforming growth factor-a were expressed by both MMC and normal plasma-cells. Using real-time polymerase chain reaction, we found HB-EGF, amphiregulin, neuregulin-1 and epiregulin to be expressed by cells from the bone marrow-environment. Only the EGF-members able to bind heparan-sulphate proteoglycans (HSPGs) -neuregulin-1, amphiregulin, HB-EGF -promote the growth of MMC. Those ligands strongly bind MMC through HSPGs. The binding and the MMC growth activity was abrogated by heparitinase, heparin or deletion of the HS-binding domain. The number of HS-binding EGF ligand molecules bound to MMC was higher than 10 5 molecules/cell and paralleled that of syndecan-1. Syndecan-1, the main HSPG present on MM cells, likely concentrates high levels of HS-binding-EGF-ligands at the cell membrane and facilitates ErbB-activation. Altogether, our data further identify EGF-signalling as promising target for MM-therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Heparan sulfate proteoglycans (HSPGs) are present on the cell surface or secreted extracellularly where they play a variety of biological roles (Bernfield et al, 1999;Esko and Selleck, 2002;Kramer and Yost, 2003;Hacker et al, 2005). HSPGs are composed of a core protein to which repeating units of alternating glucuronic acid andNacetyl glucosamine resides are attached.…”

Section: Introductionmentioning

confidence: 99%

Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: II. The 6‐O‐sulfotransferase family

Cadwallader

Yost

2006

Developmental Dynamics

View full text Add to dashboard Cite

Heparan sulfate (HS) is an unbranched chain of repetitive disaccharides, which specifically binds ligands when attached to the cell surface or secreted extracellularly. HS chains contain sulfated domains termed the HS fine structure, which gives HS specific binding affinities for extracellular ligands. HS 6-Osulfotransferases (6-OST) catalyze the transfer of sulfate groups to the 6-O position of glucosamine residues of HS. We report here the characterization and developmental expression analysis of the 6-OST gene family in the zebrafish. The zebrafish 6-OST gene family consists of four conserved vertebrate orthologues, including a gene duplication specific to zebrafish. We examined the mRNA expression patterns in several tissues/organs throughout early zebrafish development, including early cleavage stages, eyes, somites, brain, internal organ primordial, and pectoral fin development. Members of the 6-OST gene family have spatially and temporally distinct restricted expression, suggesting in vivo functional differences exist between members of this family. Developmental Dynamics 235:3432-3437, 2006.

show abstract

“…These include growth factors, chemokines, cytokines, and enzymes that are essential for angiogenesis, cell adhesion, and locomotion. 3 Accordingly, enzymatic degradation of heparan sulfate may play a critical role in cancer cell invasion and metastasis. Heparanase is an endoglycosidase that cleaves heparan sulfate side chains of heparan sulfate proteoglycans at a limited number of sites, thus facilitating disassembly of the extracellular matrix and enhancing cell invasion.…”

mentioning

confidence: 99%

Positive association of heparanase expression with tumor invasion and lymphatic metastasis in gastric carcinoma

Wang

Jiang

et al. 2005

Modern Pathology

View full text Add to dashboard Cite

Tumor invasion and metastasis are the most common causes of death in gastric carcinoma. Human heparanase influences tumor invasiveness and angiogenesis. Analysis of its expression in gastric carcinoma has been hindered by our inability to procure pure cancer cells from heterogeneous tissue. In the present study, we analyzed heparanase expression in human primary and metastatic gastric carcinoma cells as well as in paired normal gastric epithelial cells by laser capture microdissection coupled with reverse transcriptionpolymerase chain reaction (RT-PCR). Tumor tissues, metastatic lymph nodes, and apparently uninvolved normal gastric tissues were collected from 30 patients who had undergone gastrectomy with radical lymph node dissection for gastric carcinoma without preoperative treatment. Bulk tissues and laser capture microdissected cell groups were separately subjected to RT-PCR analysis with heparanase-specific primers. For bulk tissues, heparanase-specific transcripts were detectable in all primary tumor tissues, metastatic lymph nodes, and almost all matching normal tissues. RT-PCR analysis after laser capture microdissection showed no detectable heparanase expression in matching normal epithelial cell groups. Of the laser capture microdissected primary gastric carcinoma cells, 47% (14/30) were heparanase positive. Expression was closely associated with greater tumor invasiveness, including Borrmann gross type and depth of wall infiltration. For metastatic cell groups dissected from lymph nodes, 95% showed clear heparanase expression. Furthermore, the extent of lymphatic spread was directly correlated to heparanase expression at the primary site. In conclusion, laser capture microdissection coupled with RT-PCR is a reliable approach for molecular analysis of heparanase expression in gastric carcinoma. Heparanase may facilitate invasion and metastasis of gastric carcinoma cells. Keywords: gastric carcinoma; laser capture microdissection; lymphatic metastasis; heparanase expression It is generally accepted that the invasion of the basement membrane and extracellular matrix is one of the critical steps for cancer cell metastasis. 1 Heparan sulfate proteoglycans, composed of a protein core covalently linked to heparan sulfate side-chains, represent a principal component of the extracellular matrix and, in particular, basement membranes. Cell surface heparan sulfate can also serve as coreceptors, along with the other cell surface molecules, to form functional receptor complexes that facilitate signal transduction. 2 Furthermore, heparan sulfate chains bind a large number of bioactive molecules and regulate their availability and function. These include growth factors, chemokines, cytokines, and enzymes that are essential for angiogenesis, cell adhesion, and locomotion. 3 Accordingly, enzymatic degradation of heparan sulfate may play a critical role in cancer cell invasion and metastasis. Heparanase is an endoglycosidase that cleaves heparan sulfate side chains of heparan sulfate proteoglycans at a limited number ...

show abstract

Functions of Cell Surface Heparan Sulfate Proteoglycans

Cited by 2,487 publications

References 261 publications

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: II. The 6‐O‐sulfotransferase family

Positive association of heparanase expression with tumor invasion and lymphatic metastasis in gastric carcinoma

Contact Info

Product

Resources

About