Investigation of the expression of the EphB4 receptor tyrosine kinase in prostate carcinoma

Lee, Yen-Ching; Perren, Janeanne R; Douglas, Evelyn; Raynor, Michael P; Bartley, Maria A; Bardy, Peter; Stephenson, Sally‐Anne

doi:10.1186/1471-2407-5-119

Cited by 44 publications

(36 citation statements)

References 32 publications

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“…The Eph receptors are the largest family of tyrosine kinases, comprising of 15 individual members, divided into EphA and EphB classes. Recently, several studies have documented high expression of the Eph family of receptor tyrosine kinases in tumours (Stephenson et al, 2001;Berclaz et al, 2003;Wu et al, 2004Wu et al, , 2006Lee et al, 2005;Xia et al, 2005Xia et al, , 2006Kumar et al, 2006;Masood et al, 2006). Although there is limited data on the protein levels of EphB4 in cancers, only recently, data on the biological significance of this protein in tumour biology is being accrued.…”

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confidence: 99%

The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome

et al. 2007

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EphB4 is a member of the largest family of transmembrane receptor tyrosine kinases and plays critical roles in axonal pathfinding and blood vessel maturation. We wanted to determine the biological role of EphB4 in ovarian cancer. We studied the expression of EphB4 in seven normal ovarian specimens and 85 invasive ovarian carcinomas by immunohistochemistry. EphB4 expression was largely absent in normal ovarian surface epithelium, but was expressed in 86% of ovarian cancers. EphB4 expression was significantly associated with advanced stage of disease and the presence of ascites. Overexpression of EphB4 predicted poor survival in both univariate and multivariate analyses. We also studied the biological significance of EphB4 expression in ovarian tumour cells lines in vitro and in vivo. All five malignant ovarian tumour cell lines tested expressed higher levels of EphB4 compared with the two benign cell lines. Treatment of malignant, but not benign, ovarian tumour cell lines with progesterone, but not oestrogen, led to a 90% reduction in EphB4 levels that was associated with 50% reduction in cell survival. Inhibition of EphB4 expression by specific siRNA or antisense oligonucleotides significantly inhibited tumour cell viability by inducing apoptosis via activation of caspase-8, and also inhibited tumour cell invasion and migration. Furthermore, EphB4 antisense significantly inhibited growth of ovarian tumour xenografts and tumour microvasculature in vivo. Inhibition of EphB4 may hence have prognostic and therapeutic utility in ovarian carcinoma.

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confidence: 99%

The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome

et al. 2007

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“…9,12,13 This hypothesis is supported by the observation that the soluble monomeric form of the extracellular domain of EphB4 receptor (sEphB4) that blocks EphrinB2 interaction with its cognate receptors, blocks bidirectional signaling and inhibits angiogenesis at sites of neovascularization in the adult. 14 -16 Human tumor tissue analysis has shown that EphB4 is overexpressed in many tumor types: breast, 17 colon, 18 -20 bladder, 21 endometrium, 22 head and neck, 23 prostate, 24,25 and ovary. 26,27 EphB4 directly supports tumor cell survival by inhibiting apoptosis in many of these cancers.…”

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confidence: 99%

Novel EphB4 Monoclonal Antibodies Modulate Angiogenesis and Inhibit Tumor Growth

Krasnoperov

Kumar

Ley

et al. 2010

The American Journal of Pathology

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EphB4 receptor tyrosine kinase and its cognate ligandEphrinB2 regulate induction and maturation of newly forming vessels. Inhibition of their interaction arrests angiogenesis, vessel maturation, and pericyte recruitment. In addition, EphB4 is expressed in the vast majority of epithelial cancers and provides a survival advantage to most. Here, we describe two anti-EphB4 monoclonal antibodies that inhibit tumor angiogenesis and tumor growth by two distinct pathways. MAb131 binds to fibronectin-like domain 1 and induces degradation of human EphB4, but not murine EphB4. MAb131 inhibits human endothelial tube formation in vitro and growth of human tumors expressing EphB4 in vivo. In contrast, MAb47 targets fibronectin-like domain 2 of both human and murine EphB4 and does not alter EphB4 receptor levels, but inhibits angiogenesis and growth of both EphB4-positive and EphB4-negative tumors in a mouse s.c. xenograft model. Combination of MAb47 and bevacizumab enhances the antitumor activity and induces tumor regression. Indeed, humanized antibodies hAb47 and hAb131 showed similar affinity for EphB4 and retained efficacy in the inhibition of primary tumor development and experimental metastasis.

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“…This suggests the intriguing possibility that EphB2 may have a different role in prostate cancer compared to the related EphB3 and EphB4 receptors. Indeed, recently published data indicate that EphB4 may have a tumor-promoting role in prostate cancer (Lee et al, 2005;Xia et al, 2005). These studies, however, did not examine the effects of ephrin ligand stimulation on the tumorigenic activity of EphB4.…”

Section: Bodymentioning

confidence: 88%

“…Our hypothesis is that signaling pathways activated by EphB2, and possibly other Eph receptors, negatively regulate the malignant properties of prostate cancer cells. Importantly, since submission of this application several reports have appeared in the literature highlighting the potentially critical role of different Eph receptors in the pathogenesis of prostate cancer Lee et al, 2005;Xia et al, 2005). We compared the levels of expression of several Eph receptors and ephrin ligands in non-transformed BPH-1 prostate epithelial cells and in three well characterized prostate cancer cell lines (DU145, PC3 and LNCaP) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Tumor Suppressor Activity of the EphB2 Receptor in Prostate Cancer

Pasquale¹

2007

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Investigation of the expression of the EphB4 receptor tyrosine kinase in prostate carcinoma

Abstract: Background: The EphB4 receptor tyrosine kinase has been reported as increased in tumours originating from several different tissues and its expression in a prostate cancer xenograft model has been reported.

Cited by 44 publications

References 32 publications

The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome

The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome

Novel EphB4 Monoclonal Antibodies Modulate Angiogenesis and Inhibit Tumor Growth

Tumor Suppressor Activity of the EphB2 Receptor in Prostate Cancer

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