EphA2 Expression Is Associated with Aggressive Features in Ovarian Carcinoma

Thaker, Premal H.; Deavers, Michael T.; Celestino, Joseph; Thornton, Angela; Fletcher, Mavis S.; Landen, Charles N.; Kinch, Michael S.; Kiener, Peter A.; Sood, Anil K.

doi:10.1158/1078-0432.ccr-03-0589

Cited by 194 publications

(185 citation statements)

References 44 publications

Supporting

Mentioning

174

Contrasting

Order By: Relevance

“…EphA2 overexpression has been reported to correlate with aggressive features in other human tumor types [10][11][12][13][14][15][16][17][18][19]. Consistent with these reports, we found a significant increase in EphA2 expression in pancreatic cancers as compared to benign ducts and PanIN lesions, as well as increased expression in poorly differentiated carcinomas compared to well or moderate differentiated carcinomas (P < 0.005).…”

Section: Discussionsupporting

confidence: 90%

“…Instead, ephrinA binding seems to regulate EphA2 subcellular localization and interaction with other downstream signaling proteins including FAK and the MAP/ERK signaling pathways [8,9]. EphA2 is overexpressed in a variety of human cancers, and high levels of EphA2 are associated with aggressive disease and poor clinical outcomes [10][11][12][13][14][15][16][17][18][19]. In vitro studies have shown that EphA2 is a powerful oncoprotein, sufficient to confer malignant potential on non-transformed epithelial cells [7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Mudali

Lakkur

et al. 2006

Clin Exp Metastasis

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

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

View full text Add to dashboard Cite

show abstract

“…The percentage of positive tumor cells was defined using the following scores: 0=0-5%, 1=6-25%, 2=26-50%, 3=51-75%, 4=76-100%. The final immunoreactive score was determined by the sum of both points: 0-1: negative expression (-), 2-3: weak expression (+), 4-5: moderate expression (++), 6-7: strong expression (+++) (Thaker et al, 2004;Ito et al, 2006).…”

Section: Immunohistochemistry and Immunocytochemistrymentioning

confidence: 99%

MAGED4 Expression in Glioma and Upregulation in Glioma Cell Lines with 5-Aza-2'-Deoxycytidine Treatment

Zhang¹,

Shen²,

Xie³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.

show abstract

“…[14][15][16] We have previously demonstrated that EphA2 is overexpressed in 76% of epithelial ovarian cancers. 17 This increased expression was associated with high tumor grade and stage as well as decreased overall survival. 17 We have also demonstrated that increased EphA2 expression in ovarian cancer samples is strongly associated with critical factors involved in angiogenesis and invasion such as greater microvessel density and higher matrix metalloproteinase (MMP) expression.…”

Section: Introductionmentioning

confidence: 97%

“…17 This increased expression was associated with high tumor grade and stage as well as decreased overall survival. 17 We have also demonstrated that increased EphA2 expression in ovarian cancer samples is strongly associated with critical factors involved in angiogenesis and invasion such as greater microvessel density and higher matrix metalloproteinase (MMP) expression. 18 Based on the high frequency of EphA2 overexpression and its association with aggressive tumor features, we and others have employed either agonist antibodies or in vivo siRNA to decrease EphA2 levels.…”

Section: Introductionmentioning

confidence: 97%

EphA2 overexpression promotes ovarian cancer growth

Lü

Shahzad

Wang

et al. 2008

Cancer Biology & Therapy

Self Cite

View full text Add to dashboard Cite

Background: Silencing EphA2 has been shown to result in anti-tumor efficacy. However, it is not known whether increasing EphA2 expression specifically results in increased tumor growth and progression. We examined the effects of stable EphA2 transfection into poorly invasive ovarian cancer cells with regard to in vitro invasive and in vivo metastatic potential.Results: In low cell density, EphA2-overexpressing A2780 cells (A2780-EphA2) displayed less cell-cell contact, increased cell-extracellular matrix (ECM) attachment and anchorage-independent cell growth compared to empty vector controls. There was no significant effect on anchorage-dependent cell proliferation, migration or invasion. Increased expression of EphA2 promoted tumor growth and enhanced the metastatic potential in A2780-EphA2 human ovarian cancer xenografts. The overexpression of EphA2 resulted in enhanced microvessel density (MVD), but had no effect on tumor cell proliferation.Methods: EphA2 gene was introduced into A2780 cells by retroviral infection. The effects of increased EphA2 expression were examined on cellular morphology, and anchorage-dependent and independent cell growth. Furthermore, the effect of EphA2 overexpression on metastatic ability was determined using an orthotopic nude mouse model of ovarian carcinoma.Conclusions: EphA2 promotes tumor growth by enhancing cell-ECM adhesion, increasing anchorage-independent growth and promoting angiogenesis.

show abstract

EphA2 Expression Is Associated with Aggressive Features in Ovarian Carcinoma

Cited by 194 publications

References 44 publications

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

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

MAGED4 Expression in Glioma and Upregulation in Glioma Cell Lines with 5-Aza-2'-Deoxycytidine Treatment

EphA2 overexpression promotes ovarian cancer growth

Contact Info

Product

Resources

About