Matrix heparan sulphate, but not endothelial cell surface heparan sulphate, is degraded by highly metastatic mouse lymphoma cells

Hennes, R.; Frantzen, F; Keller, R.; Schirrmacher, Volker; Schwartz‐Albiez, Reinhard

doi:10.1038/bjc.1988.189

Cited by 7 publications

(2 citation statements)

References 17 publications

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“…Indeed, heparanase activities secreted from platelets, neutrophils, or lymphoma cells were found to be able to liberate bFGF bound to matrix proteoglycans (18) or human endothelial cell perlecan (50). Although the difference in the effect of bFGF may be the result of distinct specificities between intracellular and extracellular heparanases (2,25,51) or may arise from structural differences among different HSPGs (44,52,53), it could also indicate that the in vitro inhibition we have observed may not be physiologically relevant.…”

Section: Fig 6 Bfgf Protects Octa-and Tetradecasaccharides Frommentioning

confidence: 77%

The Interaction between Basic Fibroblast Growth Factor and Heparan Sulfate Can Prevent the in Vitro Degradation of the Glycosaminoglycan by Chinese Hamster Ovary Cell Heparanases

Tumova

Bame

1997

Journal of Biological Chemistry

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Heparan sulfate proteoglycans on Chinese hamster ovary (CHO) cell surfaces can bind and internalize basic fibroblast growth factor (bFGF). We have investigated whether this interaction affects heparan sulfate catabolism in vitro by measuring the ability of partially purified CHO heparanase activities to degrade 35 S-labeled heparan sulfate glycosaminoglycans in the absence or presence of bFGF. Our studies show that the presence of the growth factor prevents partially purified heparanases from degrading the nascent 81-kDa chains to short 6-kDa products, whether the glycosaminoglycan is free in solution or covalently bound to core proteins. A 30 -60 molar excess of the growth factor is required to inhibit completely chain degradation by heparanases, implying that multiple bFGF molecules must be bound to the glycosaminoglycan to prevent heparanase-catalyzed catabolism. This hypothesis is supported by protection studies indicating that nascent CHO heparan sulfate glycosaminoglycans have at least four to eight bFGF binding sites/chain. It does not appear, however, that the growth factor inhibits heparanase-catalyzed degradation of the glycosaminoglycan by binding to the sequence cleaved by the enzyme. Both the nascent and short chains bind bFGF with similar affinity (K d values of 27.0 ؎ 3.5 and 38.9 ؎ 5.1 nM, respectively), indicating that heparanase activities do not destroy the bFGF binding sites. Rather, our results suggest that the growth factor interferes sterically with heparanase action by binding the heparan sulfate chain at a sequence next to the cleavage site or at a secondary site recognized by the enzyme.Heparan sulfate proteoglycans (HSPGs), 1 molecules composed of heparan sulfate (HS) glycosaminoglycan chains covalently linked to a protein core, are ubiquitously present on cell surfaces and in extracellular matrix and basement membranes (1-3). Their expression appears to be developmentally regulated (4, 5) and cell-specific (6). Proteoglycans are implicated in a number of cellular processes, including cell adhesion, migration, differentiation, and proliferation (for review, see Refs. 7 and 8). Most of the identified proteoglycan functions are attributed to the interaction of the glycosaminoglycan chain with a protein ligand, such as lipoprotein lipase, fibronectin, or various members of heparin-binding growth factor family (9). The last has received a great deal of attention after the presence of heparin or heparan sulfate had been shown to be prerequisite for high affinity binding of basic fibroblast growth factor (bFGF) to its cell surface fibroblast growth factor receptor (FGFR) (10 -12). It was thought originally that binding to HS might change the growth factor conformation so that it can be recognized by the FGFR; however, cocrystallization of bFGF with heparin oligosaccharides demonstrated no structural changes in the growth factor upon the binding (13). Since heparin can form a ternary complex with bFGF and FGFR (14 -16), it has been proposed that the proteoglycans function as a coreceptor for ...

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Section: Fig 6 Bfgf Protects Octa-and Tetradecasaccharides Frommentioning

confidence: 77%

The Interaction between Basic Fibroblast Growth Factor and Heparan Sulfate Can Prevent the in Vitro Degradation of the Glycosaminoglycan by Chinese Hamster Ovary Cell Heparanases

Tumova

Bame

1997

Journal of Biological Chemistry

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“…Soft agar (anchorage-independent) growth is considered to correlate well with tumorigenicity in vivo (Kahn and Shin, 1979). Several investigators have observed either tumor regression induced with heparin (Folkman et al, 1983;Coombe et al, 1987) or increased degradation of matrix related GAGS, such as heparan sulfate, by highly metastatic malignancies (Nakajima et al, 1983;Hennes et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Modulation of growth of human carcinoma SW‐13 cells by heparin and growth factors

Halper

Carter

1989

Journal Cellular Physiology

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This study reports on the effects of heparin, basic and acidic fibroblast growth factors (bFGF and aFGF, respectively), and transforming growth factor type-e (TGFe) on the growth of a human adrenocortical carcinoma cell line, SW-13. Heparin has previously been shown to inhibit growth in several cell types, including smooth muscle cells, certain fibroblasts, and epithelial cells, and to modulate the effects of fibroblast growth factors. Whereas bFGF and aFGF bind tightly to heparin and elute from a heparin-Sepharose column with 2 M NaCl and 1.6 M NaCl, respectively, TGFe binds to heparin with lower affinity and can be eluted from heparin-Sepharose column with 0.5 M NaCl. TGFe is a polypeptide unrelated to FGF, is present in neoplastic and nonneoplastic tissues, and stimulates the growth of certain epithelial cells and fibroblasts in soft agar and monolayer. Since the growth of SW-13 cells is stimulated by TGFe and by bFGF, we hypothesized that heparin would inhibit the growth of SW-13 cells by binding to these growth factors and that the effects of heparin could be overcome with the addition of either growth factor. Our experiments confirmed that heparin inhibits the growth of SW-13 cells. A dose-dependent growth inhibition was observed in both monolayer and soft agar. The inhibition in monolayer was partially reversed upon heparin withdrawal. The effects of heparin in both monolayer and soft agar were at least partially overcome by TGFe and by basic or acidic FGF. Overall protein synthesis does not appear to be affected by heparin as measured by [35S]methionine uptake. In contrast, epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) were unable to overcome heparin-induced inhibition both in monolayer and in soft agar. Heparin also inhibited [3H]thymidine incorporation in AKR-2B and partially inhibited AKR-2B cell stimulation by TGFe; however, it further potentiated the already potent stimulation by bFGF. We propose that heparin, TGFe, bFGF, and aFGF modulate the growth of SW-13 cells and possibly of other epithelial cells in complex ways and that heparin-like substances present in the extracellular matrix play an important role in the control of epithelial growth.

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Proteoglycans in Cellular Recognition and Secretory Functions in the Haemopoietic System

Ranson¹,

Gallagher

1992

Modern Trends in Human Leukemia IX

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Matrix heparan sulphate, but not endothelial cell surface heparan sulphate, is degraded by highly metastatic mouse lymphoma cells

Cited by 7 publications

References 17 publications

The Interaction between Basic Fibroblast Growth Factor and Heparan Sulfate Can Prevent the in Vitro Degradation of the Glycosaminoglycan by Chinese Hamster Ovary Cell Heparanases

The Interaction between Basic Fibroblast Growth Factor and Heparan Sulfate Can Prevent the in Vitro Degradation of the Glycosaminoglycan by Chinese Hamster Ovary Cell Heparanases

Modulation of growth of human carcinoma SW‐13 cells by heparin and growth factors

Proteoglycans in Cellular Recognition and Secretory Functions in the Haemopoietic System

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