Eph receptors and ephrin ligands: embryogenesis to tumorigenesis

Dodelet, Vincent C.; Pasquale, Elena B.

doi:10.1038/sj.onc.1203856

Cited by 275 publications

(208 citation statements)

References 71 publications

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“…EphA2, which was expressed in 7 of 15 BSG and all 12 NBSG cases in the current study, is a tyrosine kinase receptor that plays a role in carcinogenesis [27,28]. In normal cells, EphA2 localizes to sites of cell-to-cell contact [29,30], where it may negatively regulate cell growth.…”

Section: Discussionmentioning

confidence: 55%

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

et al. 2008

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We investigated the protein expression of three glioma-associated antigens (GAAs) in pediatric brain stem glioma (BSG) and non-brain stem glioma (NBSG) cases with a view to their possible use in immunotherapy. Expression of EphA2, IL-13Rα2 and Survivin were studied by immunohistochemistry on paraffin-embedded tissues using a series of 15 BSG cases and 12 NBSG cases. Thirteen of 15 BSGs and all 12 NBSGs expressed at least one of GAAs; and 7 BSGs and 9 NBSGs expressed at least two of these GAAs at higher levels than non-neoplastic brain. There was no association between the tumor grade and levels of GAA expression. Although many cases demonstrated diffuse expression of GAAs throughout specimens, partial or patchy expression was noted in a small number of cases, suggesting a need for targeting multiple GAAs in immunotherapy. These results suggest that EphA2, IL-13Ralpha2 and Survivin are suitable targets for developing vaccine strategies for pediatric glioma.

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Section: Discussionmentioning

confidence: 55%

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

et al. 2008

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“…Furthermore, genetic amplification of EPHA2, albeit an uncommon finding in this study, correlates with its role as a putative oncogene for this tumor type in which it may promote angiogenesis [36], loss of growth control and contact inhibition [6,7]. Although the Eph family is among the largest receptor tyrosine kinase family in the human genome [37], the specific functions of each member remain incompletely understood. Thus, in addition to aiding our understanding of neoplasia, the patterns of activation or inactivation of Eph receptor tyrosine kinases may provide useful information regarding their role in development and growth regulation of normal tissues as well.…”

Section: Discussionmentioning

confidence: 99%

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status

Mudali

Lakkur

et al. 2006

Clin Exp Metastasis

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EphA2 is a transmembrane receptor tyrosine kinase that functions in the regulation of cell growth, survival, angiogenesis, and migration and EphA2 targeting has been proposed as a novel therapeutic strategy for neoplasms that overexpress this protein. EphA2 overexpression has been correlated with increased invasive and metastatic ability in pancreatic cancer cell lines. However, the patterns of EphA2 expression in human pancreatic cancers and associated metastases is unknown, as are the genetics of EphA2 in this tumor type. We collected clinicopathologic data and paraffin-embedded materials from 98 patients with primary and/or metastatic pancreatic cancer and performed immunohistochemical labeling for EphA2 protein. EphA2 protein immunolabeling was found in 207 of 219 samples (95%). The expression was predominantly cytoplasmic, although predominant membranous staining was observed in a minority of cases. When evaluated specifically for labeling intensity, primary and metastatic carcinomas were more strongly positive compared to benign ducts and PanIN lesions (P < 0.00001 and P < 0.01, respectively) and poorly differentiated carcinomas were more strongly positive for EphA2 than well and moderately differentiated tumors (P < 0.005). When primary carcinomas without metastatic disease were specifically compared to carcinomas with associated metastatic disease, the advanced carcinomas showed relatively less strong positive labeling for EphA2 (P < 0.008). Moreover, decreased EphA2 labeling was more commonly found in liver (P < 0.002), lung (P < 0.004) or peritoneal metastases (P < 0.01) as compared to distant lymph node metastases (P < 0.01). Genetic sequencing of the tyrosine kinase domain of EPHA2 in 22 samples of xenograft enriched pancreatic cancer did not reveal any inactivating mutations. However, EPHA2 amplification was found in 1 of 33 pancreatic cancers corresponding to a lymph node metastasis, indicating EPHA2 genomic amplification may underlie EphA2 overexpression in a minority of patients. Our data confirms that EphA2 is overexpressed in pancreatic cancer, but suggests a relative loss of EphA2 in co-existent pancreatic cancer metastases as well as a role for EPHA2 in organ specific metastasis.

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“…Many Ephs seem to be predominantly expressed in metastatic cell lines as compared to the primary tumor, and their expression levels often correlate with the grade of the tumor malignancy and invasiveness. EphB4 is expressed in all examined breast carcinoma cell lines [14] and its role in cancer is reviewed in [16]. EphB4 is particularly interesting because it has both tumor-suppressing and tumor-promoting activities, which are affected via different molecular mechanisms: the tumor suppression seems to be a result of EphB4-dpendent downregulation of Crk that lead to inhibition of cell mobility and invasion, as well as facilitation of apoptosis; the tumor promoting properties seems to result mainly from the angiogenesis-promoting EphB4 activity [16].…”

Section: New Insights Into Functions Outside Of the Nervous Systemmentioning

confidence: 99%

“…Most significantly, Ephrin-B2 is expressed in arteries, whereas its receptor, EphB4 -in veins, thus defining their boundaries during development [13]. In addition, EphB2 and ephrin-B2 mediate the interactions between the vessel endothelial cells and the adjacent mesenchymal cells [13,14]. An important new study [15] reveals that ephrin-B2 is also required for normal association between the blood-vessel endothelial cells and the supporting pericytes and vascular smooth muscle cells (mural cells).…”

Section: New Insights Into Functions Outside Of the Nervous Systemmentioning

confidence: 99%

Cell–cell signaling via Eph receptors and ephrins

Himanen

Saha

Nikolov

2007

Current Opinion in Cell Biology

227

202

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SummaryEph receptors are the largest subfamily of receptor tyrosine kinases regulating cell shape, movements and attachment. The interactions of the Ephs with their ephrin ligands are restricted to the sites of cell-cell contact since both molecules are membrane attached. This review summarizes recent advances in our understanding of the molecular mechanisms underlining the diverse functions of the molecules during development and in the adult organism. The unique properties of this signaling system that are of highest interest and have been the focus of intense investigations are as follows: (i) the signal is often simultaneously transduced in both ligand-and receptor-expressing cells, (ii) signaling via the same molecules can generate opposing cellular reactions depending on the context, and (iii) the Ephs and the ephrins are divided in two subclasses with promiscuous intra-subclass interactions, but rarely observed inter-subclass interactions.

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Eph receptors and ephrin ligands: embryogenesis to tumorigenesis

Cited by 275 publications

References 71 publications

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status

Cell–cell signaling via Eph receptors and ephrins

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