Application of Angiogenic Oligosaccharides of Hyaluronan Increases Blood Vessel Numbers in Rat Skin

Abdul, Sattar; Rooney, Paul; Kumar, Shant; Pye, David; West, David C.; Scott, Ian C.; Ledger, Philip W.

doi:10.1111/1523-1747.ep12396880

Cited by 176 publications

(113 citation statements)

References 23 publications

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“…This is in agreement with studies related to inflammation and wound healing (35)(36)(37)(38)(39)(40). SHA fragments of 3-to 10-oligosaccharide size accelerated neoangiogenesis during wound repair within 48 -72 h (35).…”

Section: Discussionsupporting

confidence: 91%

“…In agreement with our results, HMW-HA did not affect angiogenesis, even acting antiangiogenic at higher concentrations (35). Additionally, the ability of sHA, but not HMW-HA, to stimulate directly the growth and tube formation of endothelial cells was demonstrated in a number of models including chick chorioallantoic membranes, rat skin, and cryoinjured murine skin grafts (35)(36)(37). Furthermore, sHA fragments of 10-to 16-oligosaccharide size had no effect on endothelial cell proliferation (35), thus paralleling our findings that only sHA fragments of 4 -16, but not of 10 -16, oligosaccharides activate DC.…”

Section: Discussionsupporting

confidence: 89%

“…Importantly, the sHA response of DC generated from CD44-deficient mice was identical with that of DC from CD44-expressing mice, demonstrating the sHA effect to be independent of CD44. Similar conclusions were drawn when the sHA-stimulated proliferation of vascular endothelial cells was studied (35)(36)(37). Specifically, perinuclear CD44 staining of sHA-treated endothelial cells was not different from that of untreated cells (36), indicating that the sHA uptake and specific NF-B-dependent signaling was not mediated by CD44.…”

Section: Discussionsupporting

confidence: 71%

“…Similar conclusions were drawn when the sHA-stimulated proliferation of vascular endothelial cells was studied (35)(36)(37). Specifically, perinuclear CD44 staining of sHA-treated endothelial cells was not different from that of untreated cells (36), indicating that the sHA uptake and specific NF-B-dependent signaling was not mediated by CD44. The notion that sHA fragments interact with cells independent of CD44 is supported by recent findings from Culty et al (31) and Tammi et al (42).…”

Section: Discussionsupporting

confidence: 71%

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Oligosaccharides of Hyaluronan Are Potent Activators of Dendritic Cells

Termeer

Hennies

Voith

et al. 2000

The Journal of Immunology

345

242

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The extracellular matrix component hyaluronan (HA) exists physiologically as a high m.w. polymer but is cleaved at sites of inflammation, where it will be contacted by dendritic cells (DC). To determine the effects of HA on DC, HA fragments of different size were established. Only small HA fragments of tetra- and hexasaccharide size (sHA), but not of intermediate size (m.w. 80,000–200,000) or high m.w. HA (m.w. 1,000,000–600,000) induced immunophenotypic maturation of human monocyte-derived DC (up-regulation of HLA-DR, B7-1/2, CD83, down-regulation of CD115). Likewise, only sHA increased DC production of the cytokines IL-1β, TNF-α, and IL-12 as well as their allostimulatory capacity. These effects were highly specific for sHA, because they were not induced by other glycosaminoglycans such as chondroitin sulfate or heparan sulfate or their fragmentation products. Interestingly, sHA-induced DC maturation does not involve the HA receptors CD44 or the receptor for hyaluronan-mediated motility, because DC from CD44-deficient mice and wild-type mice both responded similarly to sHA stimulation, whereas the receptor for hyaluronan-mediated motility is not detectable in DC. However, TNF-α is an essential mediator of sHA-induced DC maturation as shown by blocking studies with a soluble TNFR1. These findings suggest that during inflammation, interaction of DC with small HA fragments induce DC maturation.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 71%

See 2 more Smart Citations

Oligosaccharides of Hyaluronan Are Potent Activators of Dendritic Cells

Termeer

Hennies

Voith

et al. 2000

The Journal of Immunology

345

242

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“…Although the serum level of HA is already used as an indicator of progressive malignant disease (3), its effects on in vivo angiogenesis and endothelial cell (EC) function are complex and have been reported to depend on HA concentration and molecular size (4,5). Accordingly, whereas high molecular weight HA was shown to inhibit EC functions (6), low molecular weight HA stimulated EC proliferation, tubulogenesis (6,7), and neovascularization (8). Moreover, small HA polymers efficiently regulated CD44 cell surface functional expression and promoted tumor cell migration (9).…”

mentioning

confidence: 99%

Hyaluronan Cell Surface Binding Is Induced by Type I Collagen and Regulated by Caveolae in Glioma Cells

Annabi

Thibeault

Moumdjian

et al. 2004

Journal of Biological Chemistry

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Hyaluronan (HA) is a component of the brain extracellular matrix environment that is synthesized and secreted by glioma cells. The primary cell surface receptor for HA is CD44, a membrane glycoprotein that is functionally regulated by a membrane type 1 matrix metalloproteinase (MT1-MMP). Both CD44 and MT1-MMP are partially located in Triton X-100-insoluble domains, but no functional link has yet been established between them. In the present study, we studied the regulation of HA cell surface binding in U-87 glioma cells. We show that an MMP-dependent mechanism regulates the intrinsic cell surface binding of HA as ilomastat, a broad MMP inhibitor, increased HA binding to glioma cells. HA binding was also rapidly and specifically up-regulated by 3-fold by type I collagen in U-87 cells, which also induced a significant morphological reorganization associated with the activation of a latent form of MMP-2 through a MT1-MMP-mediated mechanism. Interestingly, caveolae depletion with a cell surface cholesteroldepleting agent ␤-cyclodextrin triggered an additional increase (9-fold) in the binding of HA, in synergy with type I collagen. On the other hand, HA cell surface binding was diminished by the MEK inhibitor PD98059 and by the overexpression of a recombinant, wild type MT1-MMP, whereas its cytoplasmic-deleted form had no effect. Taken together, our results suggest that MT1-MMP regulates, through its cytoplasmic domain, the cell surface functions of CD44 in a collagen-rich pericellular environment. Additionally, we describe a new molecular mechanism regulating the invasive potential of glioma cells involving a MT1-MMP/CD44/caveolin interaction, which could represent a potential target for anti-cancer therapies.The principal molecules that have been identified in the normal brain extracellular matrix (ECM) 1 are hyaluronan (HA; also known as hyaluronic acid, hyaluronate) and chondroitin sulfate (1, 2). HA is an important glycosaminoglycan constituent believed to be implicated in angiogenesis, the formation of new blood vessels from preexisting vasculature. Although the serum level of HA is already used as an indicator of progressive malignant disease (3), its effects on in vivo angiogenesis and endothelial cell (EC) function are complex and have been reported to depend on HA concentration and molecular size (4, 5). Accordingly, whereas high molecular weight HA was shown to inhibit EC functions (6), low molecular weight HA stimulated EC proliferation, tubulogenesis (6, 7), and neovascularization (8). Moreover, small HA polymers efficiently regulated CD44 cell surface functional expression and promoted tumor cell migration (9). Astrocytic tumors of the central nervous system express CD44 among other cell adhesion receptors of the integrin or immunoglobulin superfamily. Although HA is the principal ligand of CD44, other CD44 ligands include the ECM components collagen, fibronectin, laminin, and chondroitin sulfate, whereas mucosal addressin, serglycin, osteopontin, and the class II invariant chain represent ECM-unrelat...

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Physiological concentrations of gangliosides gm1, gm2 and gm3 differentially modify basic-fibroblast-growth-factor-induced mitogenesis and the associated signalling pathway in endothelial cells

Slevin

Kumar

et al. 1999

Int. J. Cancer

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Application of Angiogenic Oligosaccharides of Hyaluronan Increases Blood Vessel Numbers in Rat Skin

Cited by 176 publications

References 23 publications

Oligosaccharides of Hyaluronan Are Potent Activators of Dendritic Cells

Oligosaccharides of Hyaluronan Are Potent Activators of Dendritic Cells

Hyaluronan Cell Surface Binding Is Induced by Type I Collagen and Regulated by Caveolae in Glioma Cells

Physiological concentrations of gangliosides gm1, gm2 and gm3 differentially modify basic-fibroblast-growth-factor-induced mitogenesis and the associated signalling pathway in endothelial cells

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