Targeted Deficiency or Cytosolic Truncation of the VE-cadherin Gene in Mice Impairs VEGF-Mediated Endothelial Survival and Angiogenesis

Carmeliet, Peter; Lampugnani, Maria Grazia; Moons, Lieve; Breviario, Ferruccio; Compernolle, Veerle; Bono, Françoise; Balconi, Giovanna; Spagnuolo, Raffaella; Oosthuyse, Bert; Dewerchin, Mieke; Zanetti, Adriana; Angellilo, Anne; Mattot, Virginie; Nuyens, Dieter; Lutgens, Esther; Clotman, Frédéric; Ruiter, Marijke; Groot, Adriana Gittenberger De; Poelmann, R. E.; Lupu, Florea; Herbert, Jean Marc; Collen, D.; Dejana, Elisabetta

doi:10.1016/s0092-8674(00)81010-7

Cited by 1,162 publications

(1,075 citation statements)

References 39 publications

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“…Strikingly, this group showed that morpholino knockdown of VE-cadherin expression selectively prevented tumor cell-induced angiogenesis by FGF2, but not normal vessel development including formation of the intersegmental and subintestinal vessels. These findings are surprising in light of the fact that VE-cadherin null mice display several vascular defects in vessel assembly that cause embryonic lethality at day 9.5 (Carmeliet et al, 1999). The apparent discrepancy in these studies may be due to differences in the vascular programs utilized by fish and mammals.…”

Section: Early Embryo Xenotransplantant Modelmentioning

confidence: 93%

Catch of the day: zebrafish as a human cancer model

2008

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Zebrafish are making big waves in the field of cancer research. The effect has been widespread and continues to gain speed as more and more cancer researchers ride the wave of zebrafish biology. This has been largely due to the development of transgenic and xenograft models of cancer, which recapitulate many aspects of different human cancers including lymphoblastic T-cell leukemia, pancreatic cancer, melanoma and rhabdomyosarcoma. These models are already being utilized by academia and industry to search for genetic and chemical modifiers of cancer with success. The attention has been further stimulated by the amenability of zebrafish to pharmacological testing and the superior imaging properties of fish tissues that allow visualization of cancer progression and angiogenesis in live animals. This review summarizes the current zebrafish models of cancer and discusses their utility in human cancer research and future directions in the field.

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Section: Early Embryo Xenotransplantant Modelmentioning

confidence: 93%

Catch of the day: zebrafish as a human cancer model

2008

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“…(Larue et al, 1994) VE-cadherin Cell-cell adhesion Total Death at E9.5, endothelial cells are assembled in vascular plexi, but their subsequent remodeling and maturation are impaired. (Carmeliet et al, 1999) L1-CAM Cell-cell adhesion Total Malformations of the nervous system, decreased nerve sensitivity, weak and uncoordinated hindlegs. (Dahme et al, 1997) Ate1 Arginyltransferase Total Embryonic lethality at E12-17 with defects in cardiovascular development and angiogenesis (Kwon et al, 2002) Calpain IV (Capn4) Protease Total Embryonic lethality at midgestation with defects in the cardiovascular system, (Arthur et al, 2000) Birth Defects Res C Embryo Today.…”

Section: Note On Nomenclaturementioning

confidence: 99%

Cell biology of embryonic migration

Kurosaka¹,

Kashina²

2008

Birth Defects Research Pt C

111

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Cell migration is an evolutionarily conserved mechanism that underlies the development and functioning of uni-and multicellular organisms and takes place in normal and pathogenic processes, including various events of embryogenesis, wound healing, immune response, cancer metastases, and angiogenesis. Despite the differences in the cell types that take part in different migratory events, it is believed that all of these migrations occur by similar molecular mechanisms, whose major components have been functionally conserved in evolution and whose perturbation leads to severe developmental defects. These mechanisms involve intricate cytoskeleton-based molecular machines that can sense the environment, respond to signals, and modulate the entire cell behavior. A big question that has concerned the researchers for decades relates to the coordination of cell migration in situ and its relation to the intracellular aspects of the cell migratory mechanisms. Traditionally, this question has been addressed by researchers that considered the intra-and extracellular mechanisms driving migration in separate sets of studies. As more data accumulate researchers are now able to integrate all of the available information and consider the intracellular mechanisms of cell migration in the context of the developing organisms that contain additional levels of complexity provided by extracellular regulation. This review provides a broad summary of the existing and emerging data in the cell and developmental biology fields regarding cell migration during development.

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“…The adherens junctional molecules, vascular endothelial cadherin (VE-cadherin) and β-catenin are important for formation of continuous monolayers, regulation of vascular permeability, endothelial survival, tubulogenesis and initiation of angiogenesis [7,8,9]. They play a key role in placental vascular development in humans, as shown by the early expression of these molecules in haemangioblasts of the first trimester placenta [10].…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial cadherin and �-catenin in human fetoplacental vessels of pregnancies complicated by Type 1 diabetes: associations with angiogenesis and perturbed barrier function

et al. 2004

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Aims/hypothesis. Increased angiogenesis of fetoplacental vessels is a feature of pregnancies complicated by Type 1 diabetes mellitus, but the underlying molecular mechanisms are unknown. This investigation tests whether the diabetic maternal environment alters the phenotypic expression of placental vascular endothelial cadherin and β-catenin, which have been implicated as key molecules in barrier formation and angiogenesis in the endothelium. Methods. Term placental microvessels from normal pregnancies (n=8) and from those complicated by Type 1 diabetes (n=8) were perfused with 76-M r dextran tracers (1 mg/ml) and subjected to immunocytochemistry, immunoblotting and microscopy. Junctional integrity, localisation and phosphorylation were investigated along with total protein levels of vascular endothelial cadherin, β-catenin and vascular endothelial growth factor. Stereological sampling and estimation tools were used to quantify aspects of angiogenesis and endothelial proliferation. Results. In the Type 1 diabetic placentae, junctional localisations of vascular endothelial cadherin and β-catenin altered significantly, with more than 50% of microvessels showing complete loss of immunoreactivity and with no overall loss of total protein. Tracer leakage was associated with these vessels. There was a two-to three-fold increase in vessels showing junctional phospho-tyrosine immunoreactivity and hyperphosphorylated β-catenin. Vascular endothelial growth factor levels were higher in these placentae. A fourfold increase in endothelial proliferation was observed, along with an increase in total length of capillaries without any change in luminal diameter. Conclusions/interpretation. Molecular perturbations of vascular endothelial cadherin and β-catenin occur in fetoplacental vessels of pregnancies complicated by Type 1 diabetes. Phosphorylation and loss of these molecules from the adherens junctional domains may be influenced in part by the elevated levels of vascular endothelial growth factor in the placenta. Perturbations of the junctional proteins may explain the observed breach in barrier integrity and may contribute to the mechanisms that drive proliferation and increases in capillary length.

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Targeted Deficiency or Cytosolic Truncation of the VE-cadherin Gene in Mice Impairs VEGF-Mediated Endothelial Survival and Angiogenesis

Cited by 1,162 publications

References 39 publications

Catch of the day: zebrafish as a human cancer model

Catch of the day: zebrafish as a human cancer model

Cell biology of embryonic migration

Vascular endothelial cadherin and �-catenin in human fetoplacental vessels of pregnancies complicated by Type 1 diabetes: associations with angiogenesis and perturbed barrier function

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