Pleiotrophin induces angiogenesis: Involvement of the phosphoinositide-3 kinase but not the nitric oxide synthase pathways

Souttou, Boussad; Raulais, Daniel; Vigny, Marc

doi:10.1002/1097-4652(2001)9999:9999<00::aid-jcp1051>3.0.co;2-f

Cited by 73 publications

(57 citation statements)

References 28 publications

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“…For instance, HARP at a concentration of 3 nM caused a 50% inhibition of VEGF 165 -induced proliferation and almost completely abolished VEGF 165 -induced migration and differentiation without affecting the behavior of unstimulated HUVEC cultured without VEGF 165 . These results contrast with those obtained previously with microvascular endothelial cells (Papadimitriou et al, 2001) or on HUVEC stimulated with partially purified supernatants of cells overexpressing HARP (Souttou et al, 2001). In agreement with our results, we have not detected in HUVEC mRNA expression of anaplastic lymphoma kinase, a receptor that transduces HARPmediated signals.…”

Section: Discussionsupporting

confidence: 72%

Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis

et al. 2004

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Heparin affin regulatory peptide (HARP) is an heparinbinding molecule involved in the regulation of cell proliferation and differentiation. Here, we report that HARP inhibited the biological activity induced by the 165-amino-acid form of vascular endothelial growth factor (VEGF 165 ) on human umbilical vein endothelial cells. Endothelial-cell proliferation induced by VEGF 165 showed about 50% inhibition in the presence of HARP in a concentration of 3 nM. In similar range of concentrations, HARP blocked tube formation induced by VEGF 165 in three-dimensional angiogenesis assay. In vivo studies showed that HARP inhibited the VEGF 165 -induced Matrigelt infiltration of endothelial cells. We then investigated the mechanisms of this inhibition and shown that HARP inhibited the binding of 125 I-VEGF 165 to the VEGF receptors of endothelial cells. Additional studies using VEGF soluble receptors indicated that binding of 125 I-VEGF 165 to kinase insert domain-containing receptor and neuropilin receptor was inhibited by HARP, but conversely the binding of 125 I-VEGF 165 to fms-like tyrosine kinase I receptor was unaffected. A competitive affinity-binding assay demonstrated that HARP interacted directly with VEGF 165 with a dissociation coefficient of 1.38 nM. Binding assay using deletion mutants of HARP revealed that the thrombospondin type-1 repeats domains were involved in this interaction. These data demonstrate for the first time that the angiogenic factor HARP can also negatively regulates the angiogenic activity of VEGF 165 .

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Section: Discussionsupporting

confidence: 72%

Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis

et al. 2004

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“…Others have reported that bacterially produced peptides and full-length pleiotrophin can induce endothelial cells to form tubes in vitro (Papadimitriou et al, 2001). Souttou et al (2001) also found migratory and tube formation effects on human umbilical vein endothelical cells treated with pleiotrophin. These findings are thus compatible with the idea that pleiotrophin can exert an angiogenic effect.…”

Section: Discussionmentioning

confidence: 88%

Expression of VEGF and pleiotrophin in deer antler

2006

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Deer antlers represent a unique model of mammalian regeneration in that they cast and fully regenerate every year. The deer antler thus provides a fascinating model of both rapid angiogenesis and chondrogenesis and the opportunity to investigate unique growth regulatory processes. One such phenomenon is the presence of vascularized cartilage in the growing antler tip-unlike other cartilage, which is typically avascular. The mechanisms by which blood vessels grow in the cartilage as well as the factors that drive antler extension at approximately 1 cm a day have been hitherto largely unknown. The aim of this study was to determine the expression of VEGF and pleiotrophin within the growing antler tip. We isolated cervine VEGF121 and VEGF165 from deer antler and found that mRNA is produced for VEGF in the precartilage and cartilage regions. By in situ hybridization, we examined whether the VEGF receptors Flt-1 and KDR are present in deer antler and found only KDR mRNA within the endothelial cells of the precartilage region. This finding is compatible with VEGF having an angiogenic effect within antler. Pleiotrophin mRNA was found in the vascular smooth muscle cells of the dermis, thus supporting a possible role in vascular growth. High levels of pleiotrophin mRNA were also detected in the precartilage region with possible implications for both angiogenesis and chondrogenesis. This is the first report of cervine angiogenic growth factors within the growing antler tip. Anat Rec Part A, 288A: 1281-1293, 2006. 2006 Key words: angiogenesis; cartilage; chondrogenesis; endothelial Systems where growth occurs at an astonishing rate such as the placenta, embryo, and deer antler can give important insights into the mechanisms involved in angiogenesis. Deer antlers are unique mammalian appendages in that they have an annual cycle of regeneration. During regeneration, the cartilage, skin, nerves, and blood vessels of the antler must grow at a rapid rate. This full regrowth occurs under conditions of low testosterone and high plasma IGF-1 during spring (Li et al., 2003). Antler grows at varying rates in different species, with growth rates reaching 12.5 mm/day in sika deer (Gao and Li, 1988), 27.5 mm/day in moose (Goss, 1970), and approximately 10 mm/day in red deer (Fennessy et al., 1991). Antler growth is driven from the tip, which consists of dermis, mesenchyme, precartilage, and the cartilage that transforms to bone and that then progressively calcifies within the antler (Fig. 1). Antlerogenic stem cells have been found to be concentrated in the reserve mesenchyme underlying the dermis (Li et al., 2002(Li et al., , 2005a. Cells from the reserve mesenchyme divide and differentiate, thus contributing chondroblasts to the precartilage region, where progressive maturation occurs. The cartilage zone contains columns of chondrocytes and large parallel vascular channels, which give a red appearance. In the region shown as the remodeling zone (Fig. 1) THE ANATOMICAL RECORD PART A 288A: 1281-1293 (2006) expand at a rapi...

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“…PTN has been reported to be mitogenic for endothelial and epithelial cells, as well as for fibroblasts (Li et al 1990;Fang et al 1992;Delbe et al 1995;Souttou et al 1997Souttou et al , 2001). However, also antiproliferative effects on chondrocytes have been reported (Tapp et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Mature PTN is a non-glycosylated, lysine-rich peptide that migrates anomalously as an 18-kDa band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (therefore also termed p18; Corbley 1997) and is derived from a 168-residue precursor with a 32 amino acid signal sequence. PTN is mitogenic for various cell types, it promotes angiogenesis, stimulates neurite outgrowth from cultured neurones, and induces cell migration (Li et al 1990;Fang et al 1992;Delbe et al 1995;Souttou et al 1997Souttou et al , 2001Rauvala et al 2000). Together with midkine (MK) it forms a family of heparin-binding proteins that are normally expressed during embryogenesis, but rarely in healthy adult tissues (Iwasaki et al 1997).…”

mentioning

confidence: 99%

Pleiotrophin, an angiogenic and mitogenic growth factor, is expressed in human gliomas

Mentlein

Held‐Feindt

2002

Journal of Neurochemistry

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Pleiotrophin (PTN) is a mitogenic/angiogenic, 15.3 kDa heparin-binding peptide that is found in embryonic or early postnatal, but rarely in adult, tissues. Since developmentally regulated factors often re-appear in malignant cells, we examined PTN expression in human glioma cell lines, cell cultures derived from solid gliomas and glioma sections. PTN mRNA or protein was detected by reverse transcriptasepolymerase chain reaction, immunohistochemistry, western blot or enzyme-linked immunoassay in all WHO III and IV grade gliomas and cells analyzed in vitro or in situ. One WHO II grade glioma investigated was PTN negative. In vitro, PTN was synthesized in perinuclear regions of glioma cells, secreted into the cultivation medium, but its production varied considerably between glioma cells cultivated from different solid gliomas or glioma cell lines. In situ, PTN expression was restricted to distinct parts/cells of the tumour. PTN did not influence the proliferation of glioma cells themselves, but stimulated [ 3 H]thymidine incorporation into DNA of microglial cells. Furthermore, in Boyden chamber assays, PTN showed a strong chemotactic effect on murine BV-2 microglial cells. PTN is supposed to be a paracrine growth/angiogenic factor that is produced by gliomas and contributes to their malignancy by targeting endothelial and microglial cells.

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Pleiotrophin induces angiogenesis: Involvement of the phosphoinositide-3 kinase but not the nitric oxide synthase pathways

Cited by 73 publications

References 28 publications

Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis

Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis

Expression of VEGF and pleiotrophin in deer antler

Pleiotrophin, an angiogenic and mitogenic growth factor, is expressed in human gliomas

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