Chorioallantoic membrane capillary bed: A useful target for studying angiogenesis and anti‐angiogenesis in vivo

Ribatti, Doménico; Vacca, Angelo; Roncali, Luisa; Burri, Peter H.; Djonov, Valentin

doi:10.1002/ar.10021

Cited by 248 publications

(183 citation statements)

References 63 publications

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“…antiangiogenic) is supported by the fact that they associate only when blood vessels are mature and stabilized. Indeed, the CAM is a well characterized developmental model in which different stages of vascular remodeling, including endothelial "coverage" by developing smooth muscle cells, have been recognized at late stages of development [10]. In addition, it is well known that Ang1 and Tie2 null mice display defects in the maturation and maintenance of the integrity of blood vessels [11].…”

Section: Discussionmentioning

confidence: 99%

A peptide from the extracellular region of the synaptic protein α Neurexin stimulates angiogenesis and the vascular specific tyrosine kinase Tie2

Graziano

Marchiò

Bussolino

et al. 2013

Biochemical and Biophysical Research Communications

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Neurexin (NRXN) and Neuroligin (NLGN) are trans-synaptic proteins involved in vascular biology. NRXN is encoded in long () and short () isoforms. We have shown that NRXNmodulates blood vessel development in synergy with VEGFA and associates with NLGN. On the other hand NRXN is also expressed in blood vessels but does not interact with NLGN or act in synergy with VEGFA, thus demonstrating a differential role. To find clues into the vascular functions of NRXN, we chose a 7 aa motif that is part of its extracellular region and was formerly selected through a proteomic search for interactors of the vascular receptor Tie2. Next we a) synthetized and modeled such peptide in order to determine its biological activity towards Tie2 in in vitro and in vivo angiogenesis assays and b) evaluated if NRXN and Tie2 physically associate in situ during vascular development. We used biochemical and cellular assays to prove that the synthetic NRXN peptide a) modulates the angiogenic phenotype of cultured endothelial cells and angiogenesis in vivo and b) efficiently stimulates Tie2 phosphorylation and downstream mediators in endothelial cells. Moreover, we show that NRXN and Tie2 can be reciprocally immunoprecipated from chicken blood vessels at late stages of vascular development. These data have a double significance, i.e. provide a novel tool to modulate Tie2 and further suggest the involvement of the NRXN family of synaptic protein in the vascular system through their interaction with a fundamental vascular player.

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Section: Discussionmentioning

confidence: 99%

A peptide from the extracellular region of the synaptic protein α Neurexin stimulates angiogenesis and the vascular specific tyrosine kinase Tie2

Graziano

Marchiò

Bussolino

et al. 2013

Biochemical and Biophysical Research Communications

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“…Here, using the chick embryo chorioallantoic membrane (CAM) assay (Ribatti et al, 2001a), we show that the ACN/IFN-g xenografts have a lower microvessel density and decreased angiogenic potential in vivo compared to vector-transfected ACN/neo cells. Moreover, the antiangiogenic activity of ACN/IFN-g xenografts affected vascular channels by increasing apoptosis of both murine and human endothelial cells, likely through nitric oxide (NO) production.…”

mentioning

confidence: 93%

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

et al. 2006

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Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-g (IFN-g) gene transfer dampens ACN tumorigenicity. As IFN-g represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-g and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-g xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-g xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-g was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds.

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“…The chorioallantoic membrane (CAM) assay, used for more than half a century, has become a mainstay in the study of blood vessel development (Auerbach et al, 2003;Cruz et al, 2000;Cruz et al, 1997;DeFouw and DeFouw, 2000a;DeFouw and DeFouw, 2000b;Djonov et al, 2000a;Djonov et al, 2000b;McDonnell et al, 2005;Rizzo and DeFouw, 1996;Rizzo et al, 1995;Rizzo et al, 1993). The CAM assay has also proved useful for biological devices and in tissue engineering applications, particularly those concerning biocompatibility studies and angiogenic responses to tissue-engineered constructs (Borges et al, 2003a;Borges et al, 2003b;Nguyen et al, 1994;Ribatti et al, 2001;Rickert et al, 2003;Valdes et al, 2003;Valdes et al, 2002;Wong et al, 2003). In this work we extend the CAM assay in the development of a histological technique to specifically examine direct vascular invasion into fibrin-based constructs.…”

Section: Introductionmentioning

confidence: 99%

Improved growth factor directed vascularization into fibrin constructs through inclusion of additional extracellular molecules

Smith

Melhem

Magge

et al. 2007

Microvascular Research

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Using the chick chorioallantoic membrane assay (CAM) and a novel histological technique we investigated the ability of blood vessels to directly invade fibrin-based scaffolds. In our initial experiments utilizing vascular endothelial growth factor (VEGF 165 ) we found no direct invasion. Instead, the fibrin was completely degraded and replaced with highly vascularized new tissue. Addition of fibroblast growth factor-2 (FGF-2), bone morphogenic protein-2 (BMP-2), or plateletderived growth factor-BB (PDGF-BB) to the fibrin construct also did not result in construct vascularization. Because natural and regenerating tissues exhibit complex extracellular matrices (ECMs), we hypothesized that a more complex scaffold may improve blood vessel invasion. Addition of fibronectin, hyaluronic acid, and collagen type I within 20 mg/mL fibrin constructs resulted in no significant improvement. However, the same additive concentrations within 10 mg/ mL fibrin constructs resulted in dramatic improvements, specifically with hyaluronic acid. Overall, we believe these results indicate the importance of structural and functional cues of not only in the initial scaffold but also as the construct is degraded and remodeled. Furthermore, the CAM assay may represent a useful model for understanding ECM interactions as well as for screening and designing tissue engineered scaffolds.

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Chorioallantoic membrane capillary bed: A useful target for studying angiogenesis and anti‐angiogenesis in vivo

Cited by 248 publications

References 63 publications

A peptide from the extracellular region of the synaptic protein α Neurexin stimulates angiogenesis and the vascular specific tyrosine kinase Tie2

A peptide from the extracellular region of the synaptic protein α Neurexin stimulates angiogenesis and the vascular specific tyrosine kinase Tie2

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

Improved growth factor directed vascularization into fibrin constructs through inclusion of additional extracellular molecules

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