Expression of receptor tyrosine kinase EphB4 and its ligand ephrin-B2 is associated with malignant potential in endometrial cancer

Takai, Noriyuki; Miyazaki, Tami; Fujisawa, Kayo; Nasu, Kaei; Miyakawa, Isao

doi:10.3892/or.8.3.567

Cited by 43 publications

(47 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Shin et al (2001) observed ephrin-B2-expressing ECs within the vasculature of tumours, and ephrin-Bs and Ephs have been found to be expressed by a variety of human solid tumours Ephrin-B2 in colorectal cancer W Liu et al and human tumour cell lines (Vogt et al, 1998;Tang et al, 1999aTang et al, , 2000Takai et al, 2001;Liu et al, 2002;Varelias et al, 2002). Overexpression of ephrin-Bs/Ephs is associated with increased tumour growth, increased tumorigenicity, and poorer prognosis in human osteosarcoma, endometrial cancer, and melanomas (Vogt et al, 1998;Takai et al, 2001;Varelias et al, 2002). Vogt et al (1998) reported that ephrin-B2 mRNA expression is higher in metastatic melanoma cell lines than in isogenic primary melanoma cell lines and higher in metastatic human tumours compared to primary melanomas.…”

Section: Discussionmentioning

confidence: 99%

Effects of overexpression of ephrin-B2 on tumour growth in human colorectal cancer

et al. 2004

View full text Add to dashboard Cite

Eph receptor tyrosine kinases (RTKs) and their membrane-bound ligands, the ephrins, are essential for embryonic vascular development. Recently, it has been demonstrated that overexpression of specific Ephs and ephrins is associated with a poor prognosis in human tumours. 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. As the Eph/ephrin system is involved in embryologic vasculogenesis and ephrin-B2 is expressed ubiquitously in all colon cancers studied in our laboratory, we hypothesised that overexpression of ephrin-B2 in colon cancer cells may induce tumour angiogenesis and increase tumour growth. To investigate this hypothesis, we stably transfected KM12L4 human colon cancer cells with ephrin-B2 to study its effect on tumour growth in vivo. We found that overexpression of ephrin-B2 markedly decreased tumour growth in a mouse xenograft model. 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. Using 51 Cr-labelled red blood cells (RBCs) to determine the functional blood volume in tumours, we demonstrated that tumours from ephrin-B2-transfected cells had significantly decreased blood volume compared with tumours from parental or vector-transfected control cells. Evaluation of in vitro parameters of cell cycle mediators demonstrated no alteration in the cell cycle. 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of overexpression of ephrin-B2 on tumour growth in human colorectal cancer

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The expression of syndecan-1 inversely correlates with metastasis and positively correlates with a more favorable prognosis in several epithelial cancers (Inki and Jalkanen, 1996;Wiksten et al, 2001). However, it is noteworthy that Eph receptors and ephrin B ligands are expressed in several cancer cell lines and tumor tissues (Tang et al, 1999) and that the expression of ephrin B2 is associated with invasion occurrence in endometrial cancer (Takai et al, 2001). Moreover, it has been reported that PDZ proteins bind and colocalize with both Eph receptors and their ephrin ligands at neuronal synapses (Torres et al, 1998) and that Eph B-ephrin B signaling plays an essential role in regulating cell migration (Klein, 2001).…”

Section: Discussionmentioning

confidence: 99%

Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines

et al. 2002

View full text Add to dashboard Cite

Two human breast cancer cell lines of di ering invasive and metastatic potential, MDA-MB-435 and MCF7, were examined using subtractive suppression hybridization in a search for any genes associated with metastasis. Of the 17 cDNAs identi®ed as being di erentially expressed genes, it was determined that syntenin was overexpressed in metastatic MDA-MB-435 cells. Expression analysis showed that the expression level of syntenin was well correlated with invasive and metastatic potential in various human breast and gastric cancer cell lines. Moreover, gastric tumor tissues exhibited a much higher syntenin mRNA expression than their normal counterparts. Syntenin-transfected MCF7 cells migrated more actively, and showed an increased invasion rate relative to vector-transfectants or parental MCF7 in vitro, without evidencing any e ect on the adhesion to ®bronectin, type I collagen and laminin. Similarly, the forced expression of syntenin to human gastric cancer cell line Az521 increased its migratory and invasive potential in vitro. Syntenin-expressing MCF7 cells were associated with the appearance of numerous cell surface extensions and with pseudopodia formation on collagen I, suggesting that syntenin may be involved in the signaling cascade to actin-reorganization. Mutation study suggested that PDZ2 domain of syntenin could be an essential role in its stimulatory e ect on the cell migration. This is the ®rst demonstration that syntenin, a PDZ motif-containing protein, can be overexpressed during the metastatic progression of human breast and gastric cancer cells and that it can function as a metastasis-inducing gene.

show abstract

“…In the present study, we have addressed the specific hypothesis that tumor cells which express EphB4 may be involved in the metastatic homing to ephrinB2-expressing vascular beds. This was an attractive hypothesis given that most human tumors express EphB4 (17)(18)(19)(20) and that distinct endothelial cell populations express ephrinB2 on their luminal aspect (28). Likewise, it has recently been reported that tumor cell-expressed EphB4 promotes metastatic dissemination (40).…”

Section: Discussionmentioning

confidence: 99%

“…The receptor EphB4 is widely expressed by human tumor cell lines (16,17). Correspondingly, a strong correlation between EphB4 expression and increased invasiveness has been reported for breast, colon, bladder, prostate, and endometrial tumors as well as for mesothelioma (17)(18)(19)(20). Manipulatory experiments have shown the protumorigenic functions of tumor cell-expressed EphB4 in different tumor models (17,18,21).…”

Section: Introductionmentioning

confidence: 99%

EphB4 Promotes Site-Specific Metastatic Tumor Cell Dissemination by Interacting with Endothelial Cell–Expressed EphrinB2

Héroult

Schaffner

Pfaff

et al. 2010

Molecular Cancer Research

View full text Add to dashboard Cite

The tyrosine kinase receptor EphB4 interacts with its ephrinB2 ligand to act as a bidirectional signaling system that mediates adhesion, migration, and guidance by controlling attractive and repulsive activities. Recent findings have shown that hematopoietic cells expressing EphB4 exert adhesive functions towards endothelial cells expressing ephrinB2. We therefore hypothesized that EphB4/ephrinB2 interactions may be involved in the preferential adhesion of EphB4-expressing tumor cells to ephrinB2-expressing endothelial cells. Screening of a panel of human tumor cell lines identified EphB4 expression in nearly all analyzed tumor cell lines. Human A375 melanoma cells engineered to express either full-length EphB4 or truncated EphB4 variants which lack the cytoplasmic catalytic domain (ΔC-EphB4) adhered preferentially to ephrinB2-expressing endothelial cells. Force spectroscopy by atomic force microscopy confirmed, on the single cell level, the rapid and direct adhesive interaction between EphB4 and ephrinB2. Tumor cell trafficking experiments in vivo using sensitive luciferase detection techniques revealed significantly more EphB4-expressing A375 cells but not ΔC-EphB4-expressing or mock-transduced control cells in the lungs, the liver, and the kidneys. Correspondingly, ephrinB2 expression was detected in the microvessels of these organs. The specificity of the EphB4-mediated tumor homing phenotype was validated by blocking the EphB4/ephrinB2 interaction with soluble EphB4-Fc. Taken together, these experiments identify adhesive EphB4/ephrinB2 interactions between tumor cells and endothelial cells as a mechanism for the site-specific metastatic dissemination of tumor cells. Mol Cancer Res; 8(10); 1297-309. ©2010 AACR.

show abstract

Expression of receptor tyrosine kinase EphB4 and its ligand ephrin-B2 is associated with malignant potential in endometrial cancer

Cited by 43 publications

References 0 publications

Effects of overexpression of ephrin-B2 on tumour growth in human colorectal cancer

Effects of overexpression of ephrin-B2 on tumour growth in human colorectal cancer

Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines

EphB4 Promotes Site-Specific Metastatic Tumor Cell Dissemination by Interacting with Endothelial Cell–Expressed EphrinB2

Contact Info

Product

Resources

About