Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth

Noren, Nicole K.; Lu, Mark; Freeman, Aaron E.; Koolpe, Mitchell; Pasquale, Elena B.

doi:10.1073/pnas.0401381101

Cited by 225 publications

(208 citation statements)

References 37 publications

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“…Also, several biomarkers examined showed correlation with effects observed in vitro, such as reduced tumor proliferative indices and induction of apoptosis in tumor cells (Figure 5d). EphB4 knockdown also significantly reduced tumor microvascular density, likely due to reduced stimulation of EphrinB2 expressed on tumor endothelial cells (Noren et al, 2004). It is therefore possible that targeting EphB4 in vivo inhibits tumor growth by two distinct and complementary mechanisms -direct inhibition of cell survival and indirect antiangiogenic effects.…”

Section: Expression Of Ephb4 In Bladder Cancermentioning

confidence: 99%

“…Consistent with this hypothesis, cell lines that coexpress the receptor and ligand when cultured in serumrich environment, express basal levels of receptor phosphorylation in the absence of exogenous ligand supplementation. In addition, a recent report by Noren et al (2004) documented that tumor cell expressed EphB4 could also interact with endothelial EphrinB2. The RT24 cell line that had no detectable EphrinB2 expression, but high levels of EphB4, also had basal receptor phosphorylation, implicating a role for ligand-independent signaling by EphB4.…”

Section: Expression Of Ephb4 In Bladder Cancermentioning

confidence: 99%

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EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival

et al. 2005

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Section: Expression Of Ephb4 In Bladder Cancermentioning

confidence: 99%

Section: Expression Of Ephb4 In Bladder Cancermentioning

confidence: 99%

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival

et al. 2005

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“…The EphB1 antibody (Santa Cruz) was detected with a secondary antigoat IgG peroxidase-conjugated antibody (Bio-Rad). The EphB2 and EphB4 antibodies were affinity purified polyclonal antibodies to glutathione S-transferase fusion proteins containing ϳ100 amino acids from the carboxyl-terminal tails of the EphB2 or EphB4 receptors (8,25) and were detected with a secondary anti-rabbit IgG peroxidase-conjugated antibody (Amersham Biosciences).…”

Section: Methodsmentioning

confidence: 99%

“…There are also many possible uses for EphB receptor antagonists, particularly in cancer therapy. For example, we have recently reported that the interplay between EphB4 expressed in breast cancer cells and ephrin-B2 expressed in the tumor vasculature promotes tumor growth by stimulating angiogenesis through signals mediated by the cytoplasmic domain of the transmembrane ephrin-B2 ligand (8). Thus, the TNYL-RAW peptide could be developed to inhibit tumor progression and other forms of pathological angiogenesis that may similarly depend on EphB4 and ephrin-B2.…”

Section: Fig 5 Peptides As Ephb Receptor-targeting Agentsmentioning

confidence: 99%

EphB Receptor-binding Peptides Identified by Phage Display Enable Design of an Antagonist with Ephrin-like Affinity

Koolpe

Burgess

Dail

et al. 2005

Journal of Biological Chemistry

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131

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The Eph receptor tyrosine kinases are overexpressed in many pathologic tissues and have therefore emerged as promising drug target candidates. However, there are few molecules available that can selectively bind to a single Eph receptor and not other members of this large receptor family. Here we report the identification by phage display of peptides that bind selectively to different receptors of the EphB class, including EphB1, EphB2, and EphB4. Peptides with the same EphB receptor specificity compete with each other for binding, suggesting that they have partially overlapping binding sites. In addition, several of the peptides contain amino acid motifs found in the G-H loop of the ephrin-B ligands, which is the region that mediates high-affinity interaction with the EphB receptors. Consistent with targeting the ephrin-binding site, the higher affinity peptides antagonize ephrin binding to the EphB receptors. We also designed an optimized EphB4-binding peptide with affinity comparable with that of the natural ligand, ephrin-B2. These peptides should be useful as selective inhibitors of the pathological activities of EphB receptors and as targeting agents for imaging probes and therapeutic drugs.

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“…EPHB4 is a member of the Eph family of receptor tyrosine kinases. Its interaction with the ligand ephrinB2 contributes to the growth of various types of tumors and can influence the clinical outcome of cancer patients (25)(26)(27). According to our data, the EPHB4-associated CpG island was hypermethylated, and the expression of the EPHB4 gene was downregulated in the HCC cell lines.…”

Section: Discussionmentioning

confidence: 62%

Array-based profiling of the differential methylation status of CpG islands in hepatocellular carcinoma cell lines

Liu

Zheng²,

Liu³

et al. 2010

Oncology Letters

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Abstract. Alterations in the DNA methylation status particularly in CpG islands are involved in the initiation and progression of many types of human cancer. A number of DNA methylation alterations have been reported in hepatocellular carcinoma (HCC). However, a systematic analysis is required to elucidate the relationship between differential DNA methylation status and the characteristics and progression of HCC. In the present study, a global analysis of DNA methylation using a human CpG-island 12K array was performed on a number of HCC cell lines of different origin and metastatic potential. Based on a standard methylation alteration ratio of ≥2 or ≤0.5, 58 CpG island sites and 66 tumor-related genes upstream, downstream or within were identified. This study showed a series of CpG island methylation alterations in the HCC cell lines. The expression of various oncogenes, tumor suppressor genes and other key genes were up-or downregulated, respectively, resulting in CpG island hypomethylation or hypermethylation accordingly. To conclude, a foundation has been provided for screening CpG island methylation profiles as HCC biological markers.

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Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth

Cited by 225 publications

References 37 publications

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival

EphB Receptor-binding Peptides Identified by Phage Display Enable Design of an Antagonist with Ephrin-like Affinity

Array-based profiling of the differential methylation status of CpG islands in hepatocellular carcinoma cell lines

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