Regulation of cell motility, morphology, and growth by sulfated glycosaminoglycans

Klebe, Robert J.; Escobedo, Laura V.; Bentley, Kevin L.; Thompson, Laura K.

doi:10.1002/cm.970060304

Cited by 20 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it was shown by in vitro studies, that the degree of sulphation of polysaccharides added to the media of cultured cells is correlated with the degree of inhibition of SV-T2 tumour cell growth (Klebe et al, 1986). Thus, highly sulphated CS together with desmoplastic changes as they occur in primary tumour lesions and in metastatic lesions may be the expression of an effort of the host tissue to inhibit tumour growth.…”

Section: The Pattern Of Mesenchymal Cs Accumulation Around Clusters Omentioning

confidence: 99%

Stromal accumulation of chondroitin sulphate in mammary tumours of dogs

1999

View full text Add to dashboard Cite

To contribute to the investigation of the composition of the extracellular matrix in epithelial tumours, mammary gland tissues of dogs (including tumours, hyperplasias and normal tissue as well as metastatic lesions in lymph nodes and lung) were studied histochemically and immunohistochemically for distribution of sulphated glycosaminoglycans (s-GAGs). The formaline-fixed tissue was stained by alcian blue at pH 5.8, using the ‘critical electrolyte concentration’ to study the degree of sulphation of s-GAGs. s-GAGs were characterized by degradation with enzymes and nitrous acid and by immunohistochemistry with two anti-chondroitin sulphate monoclonal antibodies. The light microscopic investigation of s-GAG deposits revealed a limited number of patterns of their distribution. The main s-GAGs found in the mammary gland tumours of dogs and in metastatic lesions were chondroitin sulphate (CS) and heparin/heparan sulphate (HEP/HS). CS accumulated in diffuse structures between epithelial cells as well as around clusters of tumour cells. The latter pattern, possibly representing a mesenchymal reaction to the tumour, was present in 74% of the tumours, and in 67% of these, highly sulphated CS was present. A diffuse accumulation of CS was present almost exclusively in complex and mixed tumours; because of the expression of the 3B3 epitope for CS in immature cartilage the spindle cells of complex tumours are argued to be the precursors of the cartilage in mixed tumours. HEP/HS was stored mainly in mast cells that were found in increased numbers in hyperplasias and tumours. By pretreatment of microscopic slides with chondroitinase AC or ABC immunostaining of fibronectin could be made possible in areas in which CS was abundantly present, suggesting that CS may mask fibronectin epitopes. It is concluded that CS with different degrees of sulphation is the most important s-GAG in the extracellular matrix of mammary tumours of dogs. CS and other s-GAGs accumulate at different sites and may have a different pathogenetic significance. © 1999 Cancer Research Campaign

show abstract

Section: The Pattern Of Mesenchymal Cs Accumulation Around Clusters Omentioning

confidence: 99%

Stromal accumulation of chondroitin sulphate in mammary tumours of dogs

1999

View full text Add to dashboard Cite

show abstract

“…Interestingly, not only antithrombotic functions were recorded but also a wide variety of nonanticoagulant properties of heparin were elucidated. These nonanticoagulant properties include heparin-mediated modulation of adhesion molecules, 20,21 heparin-induced release of endothelial-bound tissue factor pathway inhibitor (TFPI), 22 modulation of fibrinolytic activators such as tissue plasminogen activator, 23 the binding of chemokines and cytokines, 24 and more recently the neutralization of damage-associated molecular patterns (DAMPS). 25 Hence, heparin expresses anticoagulant and nonanticoagulant activities (►Fig.…”

Section: Heparin As a Direct And Indirect Modifier Of Coagulation Patmentioning

confidence: 99%

The Anticoagulant and Nonanticoagulant Properties of Heparin

et al. 2020

View full text Add to dashboard Cite

Heparins represent one of the most frequently used pharmacotherapeutics. Discovered around 1926, routine clinical anticoagulant use of heparin was initiated only after the publication of several seminal papers in the early 1970s by the group of Kakkar. It was shown that heparin prevents venous thromboembolism and mortality from pulmonary embolism in patients after surgery. With the subsequent development of low-molecular-weight heparins and synthetic heparin derivatives, a family of related drugs was created that continues to prove its clinical value in thromboprophylaxis and in prevention of clotting in extracorporeal devices. Fundamental and applied research has revealed a complex pharmacodynamic profile of heparins that goes beyond its anticoagulant use. Recognition of the complex multifaceted beneficial effects of heparin underscores its therapeutic potential in various clinical situations. In this review we focus on the anticoagulant and nonanticoagulant activities of heparin and, where possible, discuss the underlying molecular mechanisms that explain the diversity of heparin's biological actions.

show abstract

“…This effect of heparin correlates with its ability to inhibit arterial SMC growth in vitro (4,12,21,41,47), and is distinct from its anticoagulant action (17,33). The proliferation of other cell types such as fibroblasts, skeletal muscle cells, and tumor cell lines is also inhibited by heparin (10,24,28,33).…”

mentioning

confidence: 99%

“…ical significance because endothelial cells and postconfluent SMCs produce heparan sulfate proteoglycans that act similarly to heparin (16,28). Likewise, highly sulfated polysaccharides such as dextran sulfate and mactin can also have antiproliferative effects (33).…”

mentioning

confidence: 99%

Transforming growth factor-beta activity is potentiated by heparin via dissociation of the transforming growth factor-beta/alpha 2-macroglobulin inactive complex.

McCaffrey

Falcone

Brayton

et al. 1989

The Journal of Cell Biology

216

View full text Add to dashboard Cite

The control of smooth muscle cell (SMC) proliferation is determined by the combined actions of mitogens, such as platelet-derived growth factor, and the opposing action of growth inhibitory agents, such as heparin and transforming growth factor-beta (TGF-beta). The present studies identify an interaction between heparin and TGF-beta in which heparin potentiates the biological action of TGF-beta. Using a neutralizing antibody to TGF-beta, we observed that the short term antiproliferative effect of heparin depended upon the presence of biologically active TGF-beta. This effect was observed in rat and bovine aortic SMC and in CCL64 cells, but not in human saphenous vein SMC. Binding studies demonstrated that the addition of heparin (100 micrograms/ml) to medium containing 10% plasma-derived serum resulted in a 45% increase in the specific binding of 125I-TGF-beta to cells. Likewise, heparin induced a twofold increase in the growth inhibitory action of TGF-beta at concentrations of TGF-beta near its apparent dissociation constant. Using 125I-labeled TGF-beta, we demonstrated that TGF-beta complexes with the plasma component alpha 2- macroglobulin, but not with fibronectin. Heparin increases the electrophoretic mobility of TGF-beta apparently by freeing TGF-beta from its complex with alpha 2-macroglobulin. Dextran sulfate, another highly charged antiproliferative molecule, but not chondroitin sulfate or dermatan sulfate, similarly modified TGF-beta's mobility. Relatively high, antiproliferative concentrations of heparin (1-100 micrograms/ml) were required to dissociate the TGF-beta/alpha 2-macroglobulin complex. Thus, it appears that the antiproliferative effect of heparin may be partially attributed to its ability to potentiate the biological activity of TGF-beta by dissociating it from alpha 2-macroglobulin, which normally renders it inactive. We suggest that heparin-like agents may be important regulators of TGF-beta's biological activity.

show abstract

Regulation of cell motility, morphology, and growth by sulfated glycosaminoglycans

Cited by 20 publications

References 35 publications

Stromal accumulation of chondroitin sulphate in mammary tumours of dogs

Stromal accumulation of chondroitin sulphate in mammary tumours of dogs

The Anticoagulant and Nonanticoagulant Properties of Heparin

Transforming growth factor-beta activity is potentiated by heparin via dissociation of the transforming growth factor-beta/alpha 2-macroglobulin inactive complex.

Contact Info

Product

Resources

About