We analyzed a panel of human melanoma tumor cell lines derived from patient tissues classified as primary (either radial growth phase or vertical growth phase) and/or metastatic for the expression of EphA2 and found a correlation between increased EphA2 expression and metastatic potential.
Of 85 EEC samples, EphA2 was overexpressed in 47% of tumors and was significantly associated with high VEGF expression (p=0.001) and high MVD counts (p=0.02).
We retrospectively evaluated the expression levels of EphA2 and ephrin-A1 in surgically treated pathological (p-) stage I NSCLC tumor samples, and their relation to clinicopathologic features or postoperative prognoses.
In this study, we investigated the expression of EphA2 mRNA and protein in 90 cases of human astrocytic tumors by reverse transcription polymerase chain reaction and immunohistochemistry, respectively.
Formalin-fixed paraffin-embedded tumor specimens from 82 <i>RAS</i> wild-type (WT) metastatic colorectal cancer patients treated with FOLFIRI + cetuximab as first-line therapy in the CAPRI-GOIM trial were assessed for EPHA2 expression by immunohistochemistry and correlated with treatment efficacy.
We found that Ephrin B3 was concomitantly expressed with EphA2 and Ephrin A1 with higher Ephrin B3 levels found in non-squamous than in squamous tumors, whereas EphA2 was higher expressed in well-differentiated than in low-differentiated tumors.
Inducing EphA2 downregulation by any one of several mechanisms (antibody-mediated inhibition of signalling, antibody-mediated downregulation of total EphA2 expression and siRNA-mediated inhibition of expression) has been shown to decrease tumour growth, prolong survival and inhibit angiogenesis in multiple preclinical models of ovarian, breast and pancreatic cancer.
We conclude that receptor EphA2 activation by ephrin-A1 induces tumor suppressor gene cdx-2 expression which attenuates cell proliferation, tumor growth and thus may be a promising therapeutic target against NSCLC.
Furthermore, a single administration of S1MP loaded with-EphA2-siRNA-DOPC substantially reduced tumor burden, angiogenesis, and cell proliferation compared with a noncoding control siRNA alone (SKOV3ip1, 54%; HeyA8, 57%), with no significant changes in serum chemistries or in proinflammatory cytokines.
More importantly, high EphA2 expression was significantly associated with tumor site, T classification, clinical stage, recurrence, and lymph node metastasis, respectively.
Ephrin A2 receptor (EphA2) plays a key role in cancer, it is up-regulated in several types of tumors and the process of ligand-induced receptor endocytosis, followed by degradation, is considered as a potential path to diminish tumor malignancy.