Disease relevance of EFNB2

• This study was designed to investigate the expression of EPHB2 and its ligands, EFNB1 and EFNB2, in human gastric cancer [1].
• Prognostic significance of EPHB6, EFNB2, and EFNB3 expressions in neuroblastoma [2].
• EFNB1 mRNA was expressed in human embryonic stem (ES) cells, neural tissues, diffuse type gastric cancer, pancreatic cancer, colon cancer, brain tumors and esophageal cancer, EFNB2 mRNA in human ES cells, neural tissues and colon cancer, EFNB3 mRNA in human ES cells, neural tissues, brain tumors, pancreatic cancer and colon cancer [3].
• We conclude that increased Lerk-5 expression possibly reflects or induces an increased potential of growth, tumorigenicity, and metastatic abilities in human melanomas [4].
• Consistent with these experimental data, we found high levels of Lerk-5 mRNA expression in advanced primary malignant melanomas and metastases (n = 22) but significantly lower or undetectable mRNA expression in benign melanocytic nevi (n = 9; P < 0.001) [4].
• Ephrin B2, PGE2, and IL-17 significantly inhibited bone resorption activity in these cells [5].

High impact information on EFNB2

• The recently characterized crystal structure of the complex formed between the ligand-binding domain of EphB2 and the ectodomain of its binding partner ephrin-B2 provides an insight into the recognition and signal transduction mechanisms of this large multifunctional family of surface receptors [6].
• A three-day infusion of the ectodomain of either EphB2 or ephrin-B2 into the lateral ventricle disrupted migration of neuroblasts and increased cell proliferation [7].
• Here, we report that the EphB4 receptor can behave as a tumour suppressor in a mouse xenograft model of breast cancer when stimulated by its ligand, ephrin-B2 [8].
• These results identify Lerk2 and HtkL as potential determinants of segmental pattern in the peripheral nervous system [9].
• Interestingly, two cell lines expressing ephrin B2 were not susceptible for rNiV-EGFP, indicating that additional factors are clearly required for full NiV replication [10].

Chemical compound and disease context of EFNB2

• Expression of receptor tyrosine kinase HTK (hepatoma transmembrane kinase) and HTK ligand by human leukemia-lymphoma cell lines [11].
• Finally, ephrin-B2/Fc promoted angiogenesis in vivo in corneal neovascularization and Matrigel plug assays in adult mice, whereas LY294002 reduced angiogenesis in Matrigel that was induced by ephrin-B2/Fc [12].

Biological context of EFNB2

• Comparative genomics analyses on EFNB1, EFNB2 and EFNB3 were performed by using bioinformatics and human intelligence (humint) [3].
• The highly conserved nature of EFNB2 in humans and animals is consistent with the broad tropism exhibited by these emerging zoonotic viruses [13].
• We also showed that the activation of Notch4 is required for VEGF-induced up-regulation of ephrin B2 and the differentiation of human venous endothelial cells in vitro [14].
• Immunohistochemical staining showed that ephrin-B2 transfectants produced higher tumour microvessel density and lower tumour cell proliferation than did parental or vector-transfected control cells [15].
• Although ephrin-B2 transfection increased tumour vessel density, the decrease in blood perfusion suggests that these vessels may be 'dysfunctional'. We conclude that overexpression of ephrin-B2 suppresses tumour cell growth and vascular function in this in vivo colon cancer model [15].

Anatomical context of EFNB2

• In transgenic livers, we showed that DLL4, active Notch4, and ephrin B2 were gradually up-regulated within the hepatocarcinoma progression and expressed on tumor sinusoidal endothelial cells [14].
• Clustered soluble HTKL stimulated the proliferation of sorted HTK+ cord blood cells and a hematopoietic cell line, UT-7/EPO from which HTK was isolated [16].
• Using RNA fingerprinting, we detected increased expression of Lerk-5 mRNA in human melanocytes as a response to the tumor-promoting drug 12-O-tetradecanoylphorbol-13-acetate, which suggests a possible role of the Lerks in melanoma tumorigenesis and progression [4].
• Our group has shown that EphB and the ephrin-B subfamilies are coexpressed in human colorectal cancer, and ephrin-B2 is expressed at higher levels in human colorectal cancer than in adjacent normal mucosa [15].
• Here, we show expression of EphB6 in human thymus, as well as the expression of ephrin-B2 in both human and mouse thymus [17].

Associations of EFNB2 with chemical compounds

• Ephrin-B2 and EphB4 most frequently were expressed on the luminal surface of colon carcinoma epithelium [18].
• In addition, we show that ephrin-B2 expression is upregulated by cocaine and amphetamine in adult mice, suggesting that ephrin-B2/EphB1 interaction may play a role in drug-induced plasticity in adults as well [19].
• High concentrations of ephrin-B2 induced tyrosine phosphorylation of EphB6 through an Src family kinase activity [20].
• Cell-type specific and estrogen dependent expression of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 during mammary gland morphogenesis [21].
• We sought to develop the natural hydrogel matrix fibrin as platform for extensive interactions and continuous signaling by the vascular morphogen ephrin-B2 that normally resides in the plasma membrane and requires multivalent presentation for ligation and activation of Eph receptors on apposing endothelial cell surfaces [22].

Other interactions of EFNB2

• Ephrin-B1 and ephrin-B2 proteins are predominantly found in the developing plexiform layers, suggesting a role in the development of intraretinal connections [23].
• Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer [1].
• Taken together, these data indicate that the expression of EPHB6, EFNB2, and EFNB3 may serve as prognostic indicators of favorable NBs [24].
• These findings suggest the involvement of HTK-HTKL system in the proliferation of HTK+ hematopoietic progenitor cells in the hematopoietic environment [16].
• Moreover, when EphB4 and ephrin-B2 were expressed in neighbouring Swiss 3T3 fibroblasts, VASP and Mena co-accumulated with activated Eph receptors at protrusions formed by EphB4-expressing cells [25].

Analytical, diagnostic and therapeutic context of EFNB2

• From the conditioned medium of C-1 cells, a soluble form of ligand was purified by receptor affinity chromatography, and the isolation of full-length cDNA revealed that this ligand is identical to the human HTK ligand (HTKL) previously reported [16].
• We found that overexpression of ephrin-B2 markedly decreased tumour growth in a mouse xenograft model [15].
• Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis [26].
• Assignments of the GAS6, POSTN and EFNB2 genes to SSC11 by somatic cell and radiation hybrid panels [27].
• HTK and HTKL mRNA expression were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) [11].

References