Hyaluronectin blocks the stimulatory effect of hyaluronan‐derived fragments on endothelial cells during angiogenesis in vitro

Trochon, Véronique; Mabilat-Pragnon, C; Bertrand, Philìppe; Legrand, Yves; Soria, Jeannette; Soria, Claudine; Delpech, Bertrand; Lű, He

doi:10.1016/s0014-5793(97)01337-9

Cited by 41 publications

(23 citation statements)

References 19 publications

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“…This high-molecular-weight glycosaminoglycan, composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine, has been shown to mediate several biological functions. It has been reported that only HA fragments (6 -20 saccharide units) are responsible for endothelial-cell proliferation and migration leading to angiogenesis (West et al, 1985;West and Kumar, 1989;Trochon et al, 1997). These fragments would act by binding to the CD44 receptor exposed on the membrane of endothelial cells (Trochon et al, 1996), in agreement with the observation that testicular-hyaluronidase degradation of HA induced angiogenesis in the chick chorio-allantoic membrane assay (West et al, 1985), in rat skin (Sattar et al, 1994) and in cryo-injured skin grafts (Lees et al, 1995).…”

supporting

confidence: 66%

Apigenin inhibits endothelial-cell proliferation in G2/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression

et al. 2000

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supporting

confidence: 66%

Apigenin inhibits endothelial-cell proliferation in G2/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression

et al. 2000

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“…16 Briefly, 1.5% agarose was dissolved in the culture medium free of FCS to form a gel in the wells. Half of the agarose cylinder was then cut off from each well.…”

Section: Wound Recovery Assaymentioning

confidence: 99%

Hyaluronan oligosaccharides are potential stimulators to angiogenesis via RHAMM mediated signal pathway in wound healing

Gao¹,

Yang²,

Mo³

et al. 2008

CIM

138

104

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Clin Invest Med 2008; 31 (3): E106-E116. AbstractPurpose: To determine if oligosaccharides of hyaluronan (o-HA) promotes wound recovery by accelerating angiogenesis and to study the mechanisms by which o-HA stimulates endothelial cell (EC) proliferation. Methods: Using hyaluronidase digestion, we prepared a mixture of hyaluronan (HA) fragments sizesd 2 to 10 disaccharides units, and studied their effects on EC growth and migration in mimicking wound recovery in vitro. The effects of o-HA on EC growth in vitro were studied by counting cell numbers. The roles of 2 hyaluronan receptors on EC cells, CD44 and RHAMM (Receptor for HAMediated Motility), were studied in initiating signaling cascades, using immunoblot assay. Signal transduction was determined by blocking antibodies to CD44 and RHAMM. An in vitro wound healing model was prepared by scratching the cellular layer of cultured EC, and movement of cells into the denuded area was quantified. Results: o-HA was a strong stimulator to EC proliferation at low concentration 10 g/ml compared with native high molecular weight HA (n-HA) (P<0.01). Signal transduction may be initiated by o-HA via RHAMM receptor on EC membrane, but not CD44. In the in vitro model, the lesion area was nearly completely recovered when the EC layer was exposed to o-HA 40hrs post-injury, whereas the wound area remained half recovered pretreated with native undegraded large HA and control medium.(P <0.05 from 24 to 40hrs). Conclusion:Hyaluronan oligosaccharides may play a role in wound healing by increasing angiogenesis. o-HA-RHAMM binding dependent signal transduction pathway may be important in the regulation of angiogenesis associated with EC proliferation.

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“…To study the effect of RDD on angiogenesis, we induced HMEC-1 cells, adapted for tube-like structure formation (38), to form anastomosing networks of capillary-like tubes in a fibrin gel, as described previously (40). Cells were cultured on microcarrier beads until confluence and were then embedded a in three-dimensional fibrin gel.…”

Section: Rdd Purificationmentioning

confidence: 99%

Evidence of Antiangiogenic and Antimetastatic Activities of the Recombinant Disintegrin Domain of Metargidin

et al. 2004

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Metargidin, a transmembrane protein of the adamalysin family, and integrins, e.g., ␣5␤1 and ␣v, are preferentially expressed on endothelial cells on angiogenesis. Furthermore, metargidin interacts with these integrins via its disintegrin domain. In this study, recombinant human disintegrin domain (RDD) was produced in Escherichia coli by subcloning its cDNA into the pGEX-2T vector, and the effect of purified RDD on different steps of angiogenesis was evaluated. At concentrations of 2-10 g/ml, RDD exhibited inhibitory activities in a variety of in vitro functional assays, including endothelial cell proliferation and adhesion on the integrin substrates fibronectin, vitronectin, and fibrinogen. RDD (10 g/ ml) totally abrogated endothelial cell migration and blocked most capillary formation in a three-dimensional fibrin gel. To test RDD efficacy in vivo, the RDD gene inserted into pBi vector containing a tetracyclineinducible promoter was electrotransferred into nude mouse muscle. RDD was successfully synthesized by muscle cells in vivo as shown by immunolabeling and Western blotting. In addition, 78% less MDA-MB-231 tumor growth, associated with strong inhibition of tumor angiogenesis, was observed in athymic mice bearing electrotransferred RDD. Moreover, in the presence of RDD, 74% fewer B16F10 melanoma lung metastases were found in C57BL/6 mice. Taken together, these results identified this RDD as a potent intrinsic inhibitor of angiogenesis, tumor growth, and metastasis, making it a promising tool for use in anticancer treatment.

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Hyaluronectin blocks the stimulatory effect of hyaluronan‐derived fragments on endothelial cells during angiogenesis in vitro

Cited by 41 publications

References 19 publications

Apigenin inhibits endothelial-cell proliferation in G2/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression

Apigenin inhibits endothelial-cell proliferation in G2/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression

Hyaluronan oligosaccharides are potential stimulators to angiogenesis via RHAMM mediated signal pathway in wound healing

Evidence of Antiangiogenic and Antimetastatic Activities of the Recombinant Disintegrin Domain of Metargidin

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