EphA2 blockade enhances the anti-endothelial effect of radiation and inhibits irradiated tumor cell-induced migration of endothelial cells

Fokas, Emmanouil; Kamlah, F.; Hänze, Jörg; Engenhart‐Cabillic, Rita; Rose, Frank; An, Han‐Xiang

doi:10.1111/j.1759-7714.2010.00029.x

Cited by 10 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The switch to a lymphangiogenic phenotype in tumors is likely to require up-regulation of expression of lymphangiogenic factors and down-regulation of expression of lymphangiogenic inhibitors (Alitalo and Carmeliet 2002). Genomic instability of tumor cells can lead to expression of multiple angiogenic and lymphangiogenic factors (Fokas 2010;Cao 2005). Members of the insulin-like growth factor (IGF) family are frequently expressed in many types of tumors associated with malignant progression and poor prognosis (Cullen et al 1990;Long et al 1998;Reinmuth et al 2002;Ritter et al 2002;Tanno et al 2001;Xie et al 1999).…”

Section: Introductionmentioning

confidence: 97%

The distribution of IGF2 and IMP3 in osteosarcoma and its relationship with angiogenesis

Chen

Wang

et al. 2011

J Mol Hist

View full text Add to dashboard Cite

The aim of this study was to investigate the expression patterns of IGF2 and IMP3 in osteosarcoma as well as its relationship with angiogenesis in the tumor. IGF2 and IMP3 expression was detected by immunohistochemical staining in the serial sections of the osteosarcoma. The impacts of IGF2 and IMP3 expression patterns on tumor angiogenesis were evaluated by statistics. The IGF2 and IMP3 staining had different expression patterns in different osteosarcoma. Twelve out of the sixty-four cases of conventional osteosarcoma showed nuclear staining patterns, and twenty-nine showed cytoplasmic staining of IGF2 and IMP3 simultaneously. On the other hand, fourteen cases showed nuclear IGF2 staining but cytoplasmic IMP3 expression, and nine cases showed nuclear IMP3 staining and cytoplasmic IGF2 expression. Twenty-eight out of forty-seven cases of parosteal osteosarcoma showed nuclear IGF2 and IMP3 expression, nine showed cytoplasmic IGF2 and IMP3 expression simultaneously. Seven out of forty-seven cases of parosteal osteosarcoma expressed IGF2 with nuclear staining but expressed IMP3 with cytoplasmic staining. Meanwhile, three cases expressed IGF2 with cytoplasmic staining but expressed IMP3 with nuclear staining. Similar to the parosteal osteosarcoma, the periosteal osteosarcoma expressed IGF2 and IMP3 mainly with nuclear staining simultaneously, forty out of fifty-five cases of periosteal osteosarcoma did that. Five out of fifty-five cases expressed IGF2 and IMP3 with cytoplasmic staining at the same time. Four cases showed nuclear IGF2 staining and cytoplasmic IMP3 staining. In the parosteal and periosteal osteosarcoma, there was no significant difference in IGF and IMP3 expression patterns (P = 0.216). However, compared with conventional osteosarcoma, the parosteal and periosteal osteosarcoma showed significant difference in IMP3 and IGF2 expression (P = 0.016, P = 0.023). IGF2 and IMP3 expression patterns were positive correlation in the different osteosarcoma (r = 0.1021, P = 0.032). The Microvessel density (MVD) in osteosarcoma with IGF2 and IMP3 cytoplasmic staining was more than that with nuclear expression of IGF2 and IMP3, and the difference was significant (P = 0.024). Moreover, the conventional osteosarcoma with cytoplasmic IGF and IMP3 showed more MVD than parosteal and periosteal osteosarcoma with cytoplasmic IGF and IMP3, and the difference was significant (P = 0.035). IGF2 and IMP3 had different expression patterns, which might be associated with angiogenesis. However, cytoplasmic and nuclear expression of IGF2 and IMP3 might play different roles in the angiogenesis of osteosarcoma.

show abstract

Section: Introductionmentioning

confidence: 97%

The distribution of IGF2 and IMP3 in osteosarcoma and its relationship with angiogenesis

Chen

Wang

et al. 2011

J Mol Hist

View full text Add to dashboard Cite

show abstract

“…A previous study found that up-regulated EphA2 expression is associated with cancer lymphogenous metastasis and poor prognosis, suggesting that EphA2 contributes to cancer progression ( 9 ). Moreover, EphA2 provides a protective mechanism by which tumors can attenuate irradiation-induced antivascular effect, so that the tumors can easily migrate and escape radiation ( 10 ). A previous literature represents EphA2 as an important target of miR-26b in gliomas ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-26b Enhances the Radiosensitivity of Hepatocellular Carcinoma Cells by Targeting EphA2

Jin

Cao

2016

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Sensitizing hepatocellular carcinoma (HCC) cells to irradiation is important to achieve satisfactory therapeutic effect with low-dose radiotherapy. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) is a member of the Eph receptor family that constitutes the largest family of tyrosine kinase receptors. EphA2 overexpression is one of the poor prognostic factors in many progressive cancers. Importantly, EphA2 is a potential target of microRNA-26b (miR-26b), and miR-26b expression is downregulated in several types of cancer. In this study, we measured the expression levels of miR-26b and EphA2 protein in seven human HCC cell lines by quantitative PCR and western blot analysis, respectively. Overall, lower miR-26b expression levels tended to be associated with higher EphA2 levels in HCC cell lines. Among the cell lines examined, 97H HCC cells expressed the lowest level of miR-26b and highest level of EphA2 protein. Thus, using 97H HCC cells, EphA2 mRNA was verified as the target of miR-26b by the luciferase reporter assay. Accordingly, a synthetic miR-26b, miR-26b mimics, was used to mimic the function of endogenous miR-26b. In 97H HCC cells transfected with miR-26b mimics or short-hairpin RNA targeting EphA2 mRNA, expression of EphA2 protein was reduced, which was associated with significantly lower proliferation rate and invasion ability and with higher apoptosis rate in response to low-dose irradiation, compared to control cells. In contrast, 97H HCC cells over-expressing EphA2 showed higher proliferation rate and invasion ability and lower apoptosis rate upon irradiation. These data suggest that miR-26b enhances the radiosensitivity of 97H HCC cells by targeting EphA2 protein.

show abstract

“…This evidence indicates that upregulation of EphA2 confers properties such as increased cancer motility, invasiveness, and metastasis. Furthermore, emerging evidence shows that EphA2 blockade enhances the antiendothelial effect of radiation and inhibits irradiated tumor cell‐induced migration of endothelial cells, implying that EphA2 probably gives cancer cells an opportunity to escape radiation stress [7].…”

Section: Introductionmentioning

confidence: 99%

EphA2 modulates radiosensitive of hepatocellular carcinoma cells via p38/mitogen‐activated protein kinase‐mediated signal pathways

Jin

Cao

2015

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

This experiment was conducted to investigate the role of EPH receptor A2 (EphA2) in the modulation of radiosensitivity of hepatic cellular cancer (HCC) cells and to determine whether p38/mitogen-activated protein kinase (p38MAPK) signaling mediated EphA2 function in this respect. The protein expressions of EphA2 and phosphorylated p38MAPK were tested in HCC and normal hepatic tissues. In HCC 97H cells, EphA2 was overexpressed and knocked out by transfection with EphA2 expression vector and EphA2-ShRNA, respectively, prior to cell exposure to low-dose irradiation. Significantly upregulated EphA2 and phosphorylated p38MAPK were observed in HCC tissues, compared with those in normal hepatic tissues. Low-dose irradiation (1 Gy) only caused minor damage to HCC 97H cells, as assessed by alterations in cell viability, apoptosis rate, and cell healing capacity (p = 0.072, p = 0.078, and p = 0.069 respectively). However, EphA2 knock-out in HCC 97H cells induced significant reduction in cell viability and cell healing capacity after these cells were subjected to low-dose irradiation. Apoptosis rate underwent dramatic increase (p < 0.01). By contrast, EphA2 overexpression in HCC 97H cells reversed these effects and enhanced cell colony formation rate, thus displaying remarkable attenuation of radiosensitivity of HCC 97H cells. Further, SB203580, a specific inhibitor of p38MAPK, was added to HCC 97H cells over-expressing EphA2. The effect of EphA2 overexpression on the radiosensitivity of HCC 97H cells was abrogated. Thus, the present study indicates that EphA2 have the ability to negatively regulate the radiosensitivity of HCC 97H cells, which mainly depends on 38MAPK-mediated signal pathways.

show abstract

EphA2 blockade enhances the anti-endothelial effect of radiation and inhibits irradiated tumor cell-induced migration of endothelial cells

Cited by 10 publications

References 36 publications

The distribution of IGF2 and IMP3 in osteosarcoma and its relationship with angiogenesis

The distribution of IGF2 and IMP3 in osteosarcoma and its relationship with angiogenesis

MicroRNA-26b Enhances the Radiosensitivity of Hepatocellular Carcinoma Cells by Targeting EphA2

EphA2 modulates radiosensitive of hepatocellular carcinoma cells via p38/mitogen‐activated protein kinase‐mediated signal pathways

Contact Info

Product

Resources

About