Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alpha vbeta 3 and alpha 5beta 1 integrins

Huynh‐Do, Uyen; Stein, Elke; Lane, Andrew A.; Liu, Hua; Cerretti, Douglas Pat; Daniel, Thomas O.

doi:10.1093/emboj/18.8.2165

Cited by 189 publications

(167 citation statements)

References 34 publications

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“…Eph receptor signaling has been proposed to in¯uence the movement of neuronal growth cones and the segregation of subpopulations of cells, including endothelial cells (Adams et al, 1999;Flanagan and Vanderhaeghen, 1998;Wang et al, 1998). Eph receptor signaling in tumors may promote the migration of endothelial cells and their assembly into capillary structures by regulating cytoskeletal plasticity, matrix attachment, and/or intercellular adhesion (Huynh-Do et al, 1999;Pandey et al, 1995;Stein et al, 1998;Zisch et al, 2000). Accordingly, in vitro ephrin-A1 acts as a chemoattractant for endothelial cells (Pandey et al, 1995), consistent with a stimualtory role in vascular remodeling.…”

Section: Discussionmentioning

confidence: 77%

The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization

et al. 2000

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Eph receptor tyrosine kinases and their ephrin ligands have been implicated in embryonic vascular development and in in vivo models of angiogenesis. Eph proteins may also regulate tumor neovascularization, but this role has not been previously investigated. To screen for Eph proteins expressed in tumor blood vessels, we used tumor xenografts grown in nude mice from MDA-MB-435 human breast cancer cells or KS1767 human Kaposi's sarcoma cells. By immunohistochemistry, the ephrin-A1 ligand and one of its receptors, EphA2, were detected throughout tumor vasculature. Double-labeling with anti-CD34 antibodies demonstrated that both ephrin-A1 and EphA2 were expressed in xenograft endothelial cells and also tumor cells. Furthermore, EphA2 was tyrosinephosphorylated in the xenograft tumors, indicating that it was activated, presumably by interacting with ephrin-A1. Ephrin-A1 and EphA2 were also detected in both the vasculature and tumor cells of surgically removed human cancers. In an in vitro angiogenesis model, a dominant negative form of EphA2 inhibited capillary tube-like formation by human umbilical vein endothelial cells (HUVECs), demonstrating a requirement for EphA receptor signaling. These data suggest that ephrin-A1 and EphA2 play a role in human cancers, at least in part by in¯uencing tumor neovascularization. Eph proteins may represent promising new targets for antiangiogenic cancer treatments. Oncogene (2000) 19, 6043 ± 6052.

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Section: Discussionmentioning

confidence: 77%

The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization

et al. 2000

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“…Ephrins are known to modulate ECM/integrin-mediated adhesion (Huynh-Do et al, 1999, 2002Chong and Jiang, 2005;Prevost et al, 2005;Foo et al, 2006). Alternatively, ephrinB2 signals could affect production or secretion of fibronectin, or influence a fibronectin-selective proteinase.…”

Section: How Does Loss Of a Pdz Binding Site On Ephrinb2 Affect The Ementioning

confidence: 99%

Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity

Wilkinson

Schittny

Reinhardt

et al. 2008

Developmental Dynamics

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Alveoli are formed in the lung by the insertion of secondary tissue folds, termed septa, which are subsequently remodeled to form the mature alveolar wall. Secondary septation requires interplay between three cell types: endothelial cells forming capillaries, contractile interstitial myofibroblasts, and epithelial cells. Here, we report that postnatal lung alveolization critically requires ephrinB2, a ligand for Eph receptor tyrosine kinases expressed by the microvasculature. Mice homozygous for the hypomorphic knockin allele ephrinB2 ⌬V/⌬V , encoding mutant ephrinB2 with a disrupted C-terminal PDZ interaction motif, show severe postnatal lung defects including an almost complete absence of lung alveoli and abnormal and disorganized elastic matrix. Lung alveolar formation is not sensitive to loss of ephrinB2 cytoplasmic tyrosine phosphorylation sites. Postnatal day 1 mutant lungs show extracellular matrix alterations without differences in proportions of major distal cell populations. We conclude that lung alveolar formation relies on endothelial ephrinB2 function. Developmental Dynamics 237:2220 -2234, 2008.

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“…Besides that, EphA2 and E-cadherin may play a critical role in colorectal tumour metastasis, as their expressions have been found to correlate closely with cancer progression (Saito et al 2004). In addition to modulating cell -cell adhesion through cadherins, Eph receptor activation can also regulate integrin-mediated cell -matrix adhesion (Huynh-Do et al 1999;Miao et al 2000Miao et al , 2005. EphB2 regulates integrins through the activity of R-Ras.…”

Section: Introductionmentioning

confidence: 99%

Computational model of cell positioning: directed and collective migration in the intestinal crypt epithelium

Wong

Chiam

Lim

et al. 2010

J. R. Soc. Interface.

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The epithelium of the intestinal crypt is a dynamic tissue undergoing constant regeneration through cell growth, cell division, cell differentiation and apoptosis. How the epithelial cells maintain correct positioning and how they migrate in a directed and collective fashion are still not well understood. In this paper, we developed a computational model to elucidate these processes. We show that differential adhesion between epithelial cells, caused by the differential activation of EphB receptors and ephrinB ligands along the crypt axis, is necessary to regulate cell positioning. Differential cell adhesion has been proposed previously to guide cell movement and cause cell sorting in biological tissues. The proliferative cells and the differentiated post-mitotic cells do not intermingle as long as differential adhesion is maintained. We also show that, without differential adhesion, Paneth cells are randomly distributed throughout the intestinal crypt. In addition, our model suggests that, with differential adhesion, cells migrate more rapidly as they approach the top of the intestinal crypt. Finally, by calculating the spatial correlation function of the cell velocities, we observe that differential adhesion results in the differentiated epithelial cells moving in a coordinated manner, where correlated velocities are maintained at large distances, suggesting that differential adhesion regulates coordinated migration of cells in tissues.

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Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alpha vbeta 3 and alpha 5beta 1 integrins

Cited by 189 publications

References 34 publications

The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization

The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization

Role for ephrinB2 in postnatal lung alveolar development and elastic matrix integrity

Computational model of cell positioning: directed and collective migration in the intestinal crypt epithelium

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