Endothelial cell-derived heparan sulfate binds basic fibroblast growth factor and protects it from proteolytic degradation.

Saksela, Olli; Moscatelli, David; Sommer, Andreas; Rifkin, Daniel B.

doi:10.1083/jcb.107.2.743

Cited by 765 publications

(418 citation statements)

References 40 publications

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“…The masking of heparin-binding sites of bFGF by soluble heparan sulfate prevents bFGF from rebinding to insoluble heparan sulfate proteoglycans (Flaumenhaft et al, 1990). Because the bFGF-heparan sulfate complex maintains the same biological potency as bFGF (Moscatelli, 1987;Saksela et al, 1988), this complex functions as a diffusible form of active bFGF. Thus, diffusible forms of growth factor can be generated by solubilization of the insoluble extracellular components to which they are bound.…”

Section: Extracellular Matrixmentioning

confidence: 99%

“…The interaction of growth factors with matrix molecules can also stabilize the growth factor. For example, heparin protects aFGF and bFGF from inactivation by heat or acid (Gospodarowicz and Cheng, 1986) and proteases (Rosengart et al, 1988;Saksela et al, 1988;Sommer and Rifkin, 1989). The half-life of aFGF is increased 100-fold in the presence of heparin (Damon et al, 1989;Ortega et al, 1991).…”

Section: Extracellular Matrixmentioning

confidence: 99%

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The extracellular regulation of growth factor action.

Flaumenhaft

Rifkin

1992

MBoC

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163

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Section: Extracellular Matrixmentioning

confidence: 99%

Section: Extracellular Matrixmentioning

confidence: 99%

The extracellular regulation of growth factor action.

Flaumenhaft

Rifkin

1992

MBoC

Self Cite

163

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“…These include acidic and basic fibroblast growth factors (FGF1, FGF2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-a and -b, platelet-derived growth factor (PDGF), angiogenin, interleukin (IL)-8 and tumor necrosis factor (TNF)-a (Risau, 1995). In most cases, these growth factors are bound to the extracellular matrix and to various proteoglycans, and can be released by protease digestion (Saksela et al, 1988;Saksela and Rifkin, 1990;Whitelock et al, 1996). In fact, tumor vascularity has been shown to directly correlate with VEGF production by the tumor, indicating that VEGF production is a relevant factor in determining angiogenesis in primary tumors (Balsari et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Decorin suppresses tumor cell-mediated angiogenesis

et al. 2002

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The progressive growth of most neoplasms is dependent upon the establishment of new blood vessels, a process regulated by tumor-secreted factors and matrix proteins. We examined the in vitro and in vivo angiogenic ability of conditioned media obtained from fibrosarcoma, carcinoma, and osteosarcoma cells and their decorintransfected counterparts. Human endothelial cells were investigated in vitro by evaluating three essential steps of angiogenesis: migration, attachment, and differentiation. On the whole, wild-type tumor cell-secretions enhanced endothelial cell attachment, migration, and differentiation, whereas their decorin-expressing forms inhibited these processes. Similarly, decorin-containing media suppressed endothelial cell sprouting in an ex vivo aortic ring assay. Since angiogenesis is an important component of tumor expansion, the growth rate of these cells as tumor xenografts was examined by implantation in nude mice. In vivo, the decorin-expressing tumor xenografts grew at markedly lower rates and showed a significant suppression of neovascularization. Immunohistochemical, Northern and Western blot analyses indicated that the decorin-expressing cells produced vascular endothelial growth factor (VEGF) at markedly reduced rates vis-a´-vis their wild-type counterparts. Specificity of this process was confirmed by experiments where addition of recombinant decorin to the wild-type tumor cells caused 80 -95% suppression of VEGF mRNA and protein. These results provide a novel mechanism of action for decorin, and indicate that decorin could adversely affect in vivo tumor growth by suppressing the endogenous tumor cell production of a powerful angiogenic stimulus.

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“…plasminogen) [8]. Some of the biological effects of the ECM can be attributed to the combined action of structural adhesive macromolecules and ECM-immobilized molecules that are thereby protected and stabilized [9,10].…”

Section: Introductionmentioning

confidence: 99%

The extracellular matrix produced by bovine corneal endothelial cells contains progelatinase A

Ménashi¹,

Vlodavsky²,

Ishai-Michaeli³

et al. 1995

FEBS Letters

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Progelatinase A is a matrix metalloproteinase involved in the turnover of extracellular matrix (ECM). We report that the ECM produced by bovine corneal endothelial (BCE) cells contains progelatinase A free of tissue inhibitor of metalloproteinase (TIMP2). The matrix-bound progelatinase A can be activated by APMA to generate a 62 kDa and a 45 kDa species with enzymatic activity and is inhibited by TIMP2. The bound progelatinase can be released after treatment of the ECM with gelatinase B. These studies suggest that the ECM can function as a reservoir for progelatinase A which may be readily available for cells in processes such as metastasis, angiogenesis, inflammation and wound heating.

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Endothelial cell-derived heparan sulfate binds basic fibroblast growth factor and protects it from proteolytic degradation.

Cited by 765 publications

References 40 publications

The extracellular regulation of growth factor action.

The extracellular regulation of growth factor action.

Decorin suppresses tumor cell-mediated angiogenesis

The extracellular matrix produced by bovine corneal endothelial cells contains progelatinase A

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