Proteoglycans: Structures and Interactions

Kjellén, Lena; Lindahl, Ulf

doi:10.1146/annurev.bi.60.070191.002303

Cited by 1,739 publications

(968 citation statements)

References 2 publications

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“…These complex macromolecules are highly abundant in the extracellular matrix and are thought to play an important structural role, contributing to extracellular matrix integrity and insolubility. 3 In addition, heparan sulfate side chains can bind to a variety of biological mediators such as growth factors, cytokines and chemokines, 4,5 thus functioning as a readily available reservoir that can be liberated upon local or systemic cues. Moreover, heparan sulfate proteoglycans on the cell surface participates directly in signal-transduction cascades by potentiating the interaction between certain growth factors and their receptors.…”

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confidence: 99%

Spatial and temporal heparanase expression in colon mucosa throughout the adenoma-carcinoma sequence

Doviner

Maly

Kaplan³

et al. 2006

Modern Pathology

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Heparanase is a mammalian endo-b-D-glucuronidase that cleaves heparan sulfate side chains at a limited number of sites. Such enzymatic activity is thought to participate in degradation and remodeling of the extracellular matrix and to facilitate cell invasion associated with tumor metastasis, angiogenesis and inflammation. Traditionally, heparanase activity was well correlated with the metastatic potential of a large number of tumor-derived cell types. More recently, heparanase upregulation has been documented in an increasing number of primary human tumors, correlating with poor postoperative survival and increased tumor vascularity. Here, we employed antiheparanase 733 polyclonal antibody that preferentially recognizes the 50 kDa active heparanase subunit over the 65 kDa proenzyme, as well as anti-heparanase 92.4 monoclonal antibody that recognizes both the latent and the active enzyme, to follow heparanase expression, processing and localization throughout the adenoma-carcinoma transition of the colon epithelium. Normal (nondysplastic) mucosa of the large bowel near epithelial neoplasms, as well as areas of mild dysplasia in adenomas, exhibited a strong reactivity with antibody 733 that became even stronger in foci of moderate dysplasia. Interestingly, although reactivity with antibody 733 was markedly reduced in severe dysplasia and in colorectal carcinoma, response to antibody 92.4 exhibited the opposite trend and staining intensities increased in parallel with tumor stage, the highest being in carcinoma cells. Involvement of latent heparanase (detected by 92.4, but not by 733 antibody) in tumor progression was suggested by activation of the Akt/PKB signal transduction pathway upon heparanase overexpression or exogenous addition to HT29 human colon carcinoma cells. These results suggest that heparanase expression is induced during colon carcinogenesis, and that its processing, conformation and localization are tightly regulated during the course of colon adenoma-carcinoma progression. Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans. 1,2 Heparan sulfate proteoglycans consist of a protein core to which several heparan sulfate side chains are covalently attached. These complex macromolecules are highly abundant in the extracellular matrix and are thought to play an important structural role, contributing to extracellular matrix integrity and insolubility. 3 In addition, heparan sulfate side chains can bind to a variety of biological mediators such as growth factors, cytokines and chemokines, 4,5 thus functioning as a readily available reservoir that can be liberated upon local or systemic cues. Moreover, heparan sulfate proteoglycans on the cell surface participates directly in signal-transduction cascades by potentiating the interaction between certain growth factors and their receptors. 6-9 Heparan sulfate-degrading activity is thus expected to affect several fundamental aspects of cell behavior under normal and clinical settings. 1,2 Tr...

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confidence: 99%

Spatial and temporal heparanase expression in colon mucosa throughout the adenoma-carcinoma sequence

Doviner

Maly

Kaplan³

et al. 2006

Modern Pathology

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“…Heparan sulfate (HS) is a carbohydrate chain characterized by the presence of alternating uronic acid (D-glucuronic acid or L-iduronic acid) and D-glucosamine units (1,2). This glycosaminoglycan occurs covalently attached to specific core proteins to form heparan sulfate proteoglycan (HSPG) molecules.…”

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“…They are attached to the extracellular cell surface by glycosyl phosphatidylinositol linkages (9). Several minor membrane proteoglycans containing HS chains have been described, such as epican, betaglycan, and others (1,2). HSPGs that also occur in the basement membrane include perlecan, agrin, and type XVIII collagen (10,11).…”

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confidence: 99%

Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium

Patterson

Gardner

Shaw

et al. 2005

Arthritis & Rheumatism

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“…Two such markers, CD138 and VS38, are currently used in paraffin sections. CD138, a member of the syndecan family of integral membrane proteoglycans, is thought to orchestrate cytoadhesive signaling and plays a role in the pathogenesis of multiple myeloma and in the detection of plasmacytic differentiation (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). VS38 recognizes a transmembrane protein, p63, which resides in the rough endoplasmic reticulum and mediates increased secretory function (31)(32)(33).…”

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Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry

et al. 2001

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The gene encoding MUM1 was characterized as a possible translocation partner in chromosomal abnormalities involving a significant number of multiple myelomas. The overexpression of the MUM1 protein as a result of translocation t(6;14) (p25;q32) identified MUM1 as a putative regulatory molecule involved in B-cell differentiation and tumorigenesis. The expression of MUM1 protein in multiple myelomas supports this hypothesis. In the current study, using tissue microarray technology, we have tested the expression of the MUM1 protein in 1335 human malignancies and normal tissues. Our data show that the MUM1 protein is expressed in a wide spectrum of hematolymphoid neoplasms and in malignant melanomas but is absent in other human tumors. In addition, in tissue microarrays as well as in conventional paraffin sections, MUM1 staining was found to lack specificity in detecting plasmacytic differentiation as compared with two markers, CD138/Syndecan and VS38, commonly used in paraffin immunohistochemistry for detection of plasma cells.

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Proteoglycans: Structures and Interactions

Cited by 1,739 publications

References 2 publications

Spatial and temporal heparanase expression in colon mucosa throughout the adenoma-carcinoma sequence

Spatial and temporal heparanase expression in colon mucosa throughout the adenoma-carcinoma sequence

Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium

Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry

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