Identification of a Ca2(+)-dependent cell-cell adhesion molecule in endothelial cells.

Heimark, Ronald L.; Degner, M; Schwartz, Stephen M.

doi:10.1083/jcb.110.5.1745

Cited by 103 publications

(45 citation statements)

References 56 publications

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“…The process begins with the proliferation of proximal endothelial cells that form capillary branches, with vessel lumen forming through anastomotic connections between capillary tips (Mustonen and Alitalo, 1995;Risau, 1997). Angiogenesis also depends on adhesive interactions between vascular cells of which multiple adhesion molecules are involved, such as avb3, avb5, a5b1, and a2b1 integrins; PECAM-1; and VE-cadherin (Heimark et al, 1990;Lampugnani et al, 1991Lampugnani et al, , 1992Brooks, 1996).…”

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confidence: 99%

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

et al. 2007

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Angiogenesis and post-natal vasculogenesis are two processes involved in the formation of new vessels, and both are essential for tumour growth and metastases. We isolated endothelial cells from human blood mononuclear cells by selective culture. These blood outgrowth cells expressed endothelial cell markers and responded correctly to functional assays. To evaluate the potential of blood outgrowth endothelial cells (BOECs) to construct functional vessels in vivo, NOD-SCID mice were implanted with Lewis lung carcinoma cells subcutaneously (s.c.). Blood outgrowth endothelial cells were then injected through the tail vein. Initial distribution of these cells occurred throughout the lung, liver, spleen, and tumour vessels, but they were only found in the spleen, liver, and tumour tissue 48 h after injection. By day 24, they were mainly found in the tumour vasculature. Tumour vessel counts were also increased in mice receiving BOEC injections as compared to saline injections. We engineered BOECs to deliver an angiogenic inhibitor directly to tumour endothelium by transducing them with the gene for human endostatin. These cells maintained an endothelial phenotype and decreased tumour vascularisation and tumour volume in mice. We conclude that BOECs have the potential for tumour-specific delivery of cancer gene therapy.

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confidence: 99%

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

et al. 2007

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“…1 (6)(7)(8). This molecule is so far the only cadherin consistently organized at interendothelial adherence junctions (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

“…It was previously found that endothelial cells express a cell specific member of the cadherin family (cadherin-5 or vascular endothelial cadherin [VE-cadherin]) 1 (6)(7)(8). This molecule is so far the only cadherin consistently organized at interendothelial adherence junctions (8-10).…”

mentioning

confidence: 99%

Inhibition of cultured cell growth by vascular endothelial cadherin (cadherin-5/VE-cadherin).

Caveda¹,

Martín‐Padura²,

Navarro³

et al. 1996

J. Clin. Invest.

165

112

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In vivo, intact endothelium presents a low turnover rate, however, when junctions are disrupted cells gain the capacity to migrate and proliferate. This capacity is then lost when cell to cell contacts are reorganized (4).Endothelial cell junction components are therefore good candidates for transferring migration and growth inhibitory signals. Previous work (5) showed that protein membrane extracts from confluent endothelial cells were able to inhibit the growth of sparse endothelium but not of other cell types, suggesting the existence of membrane associated endothelial growth inhibitory proteins.It was previously found that endothelial cells express a cell specific member of the cadherin family (cadherin-5 or vascular endothelial cadherin [VE-cadherin]) 1 (6)(7)(8). This molecule is so far the only cadherin consistently organized at interendothelial adherence junctions (8-10). VE-cadherin is a constitutive component of all types of endothelia (8). As the other members of the family (11-15), VE-cadherin has adhesive properties and mediates homotypic cell adhesion (16). The intracellular domain interacts with cytoplasmic proteins called catenins (17) that transmit the adhesion signal and contribute to the anchorage of the protein to the actin cytoskeleton (18,19).In other types of tissues, cadherins can act as tumor suppressors. Reduced cadherin expression and/or activity is associated with enhanced tumor cell invasive potential and loss of differentiated characteristics (11)(12)(13)(14)(15)(18)(19)(20)(21)(22)(23). In agreement with these observations, VE-cadherin expression was found to be strongly reduced in angiosarcomas (24).In this paper we investigated the effect of VE-cadherin on cell growth. The results reported show that VE-cadherin can indeed transfer growth negative signals to the cells. This molecule can therefore contribute to density dependent inhibition of endothelial cell growth. MethodsCells. Human endothelial cells from umbilical vein (HUVEC) were isolated and cultured in M199 and 20% NCS (newborn calf serum) as previously described (8). Chinese hamster ovary (CHO) cells and mouse connective tissue fibroblast L929 cells were obtained from the American Tissue Type Collection and cultured in DMEM with 10% FCS (both from GIBCO, Life Technologies, Paisley, U.K.) (16). Full length VE-cadherin cDNA was cloned from human endothelial cells and inserted into pECE eukaryotic expression vector. CHO and L929 cells were cotransfected with pECE-VE-cadherin construct and pSV 2 neo plasmids by calcium phosphate precipitation as described (16). Control cells were transfected with empty pECE and pSV 2 neo plasmids, selected, cloned, and cultured as VE-cadherin transfectants (16). VE-cadherin expression in the clones used was comparable with that of HUVEC by Western and Northern blot analysis (16).For transfection of CHO cells with truncated VE-cadherin, full length VE-cadherin cDNA cloned in pBluescript vector (16)

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“…Adherens junctions, which are well developed in confluent ECs are dependent on cadherin-5 (VE-cadherin). 36,37,38 Preliminary immunofluorescence examination of the junctions in ECs exposed to granules using specific antibody to cadherin-5 revealed no loss of this protein from the apposing cell junctions except where the cells bordered lacunae. Detailed studies are in progress to evaluate the effects of heparin proteoglycan on EC adherens junctions with particular attention to the state of phosphorylation of the cadherin 39 and associated proteins 40 of the junctions.…”

Section: Discussionmentioning

confidence: 99%

Mast Cell Granule Heparin Proteoglycan Induces Lacunae in Confluent Endothelial Cell Monolayers

Lagunoff

Rickard

1999

The American Journal of Pathology

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The addition of rat mast cell granules to confluent bovine pulmonary artery endothelial cell monolayers resulted in the formation of numerous lacunae in the cultures. Several lines of evidence identified heparin proteoglycan as the component of the granule matrix responsible for the effect: presence of the activity in the proteoglycan fraction after chromatography of granule extracts , inhibition of granule activity by digestion with heparinase I , the failure of proteolysis of the proteoglycan fraction with proteinase K to significantly diminish its activity , and the failure of chymase and carboxypeptidase inhibitors to inhibit granule activity. The onset of hole formation was delayed for several hours after granule addition to the culture, and maximal hole formation occurred between 8 and 16 hours and was sustained as long as 24 hours. The lacunae formed by the separation of motile endothelial cells within the monolayer and was not attributable to cell contractile activity or cell loss. Time-lapse video recording showed that the holes were dynamic, individual holes expanding and regressing over a period of hours. Formation of lacunae occurred on gelatin and fibronectin surfaces alike. The presence of active chymase in the granules prevented the action of the proteoglycan. Heparin glycosaminoglycan as distinct from the proteoglycan did not similarly affect the endothelial monolayers but did block the action of granules added subsequently , indicating the likelihood of a heparin-reactive receptor or binding site.

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Identification of a Ca2(+)-dependent cell-cell adhesion molecule in endothelial cells.

Cited by 103 publications

References 56 publications

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

Inhibition of cultured cell growth by vascular endothelial cadherin (cadherin-5/VE-cadherin).

Mast Cell Granule Heparin Proteoglycan Induces Lacunae in Confluent Endothelial Cell Monolayers

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