EphA2 overexpression is associated with angiogenesis in ovarian cancer

Abstract

Fiber connections of the general visceral sensory centers in the brainstem were studied with tract‐tracing methods in a percomorph teleost, tilapia Oreochromis niloticus. General visceral afferents of the vagal nerve from abdominal viscera terminated bilaterally in the commissural nucleus of Cajal (NCC) and area postrema (AP). The NCC and AP projected bilaterally to the secondary general visceral nucleus (SVN), four diencephalic nuclei (the preglomerular general visceral nucleus [pVN], nucleus of the lateral recess, posterior thalamic nucleus, and lateral tuberal area), preoptic area, and ventral telencephalon (supracommissural, dorsal, and ventral parts) in addition to the glossopharyngeal and vagal lobes and medullary reticular formation. Injections to the SVN resulted in labeled terminals in the forebrain structures that receive fibers from the primary centers and additionally in the diffuse nucleus of the inferior lobe, lateral torus, and inferior subdivision of lateral torus. The present study suggests that the ascending general visceral projections arising from the brainstem centers in teleosts are quite similar to those in mammals and birds. Descending pathways were also notable. In addition to descending projections from the SVN and medullary structures to the primary centers, long descending pathways to the SVN, NCC, and AP were found to originate from the pVN, nucleus of the lateral recess, posterior thalamic nucleus, and preoptic area. The SVN was found to receive fibers from the ventral telencephalon as well. Therefore, the present study indicates that most of the general visceral structures in the forebrain are reciprocally connected with the brainstem centers. J. Comp. Neurol. 518:3570–3603, 2010. © 2010 Wiley‐Liss, Inc.

Deciphering the signaling events that promote melanoma tumor cell vasculogenic mimicry and their link to embryonic vasculogenesis: Role of the Eph receptors

“…In both cases, there was a significant association between increased EphA2 expression in the tumor cells with increased microvessel density. Furthermore, Lin and colleagues reported that increases in EphA2 expression and microvessel density corresponded to a decrease in patient survival (Lin et al, 2007). These data suggest that the inability of aggressive melanoma cells lacking sufficient EphA2 to form tumors in mice may be due to impaired tumor neovascularization, especially given previous reports that firmly establish a role for EphA2 in mediating angiogenesis in conjunction with the inability of these cells to undergo VM in vitro.…”

“…Recently, there have been reports attempting to investigate a correlation between EphA2 and microvessel density in both colorectal and ovarian carcinomas (Kataoka et al, 2004;Lin et al, 2007). In both cases, there was a significant association between increased EphA2 expression in the tumor cells with increased microvessel density.…”

EphA2 overexpression promotes ovarian cancer growth

“…44 EphA2 has been also shown to promote tumorigenesis by enhancing angiogenesis. The effects on angiogenesis may be direct (EphA2 overexpression has been noted in angiogenic blood vessels and may contribute to vasculogenic mimicry) 18 or indirect (role in VEGF mediated angiogenesis). 45,46 In the present study, we found that EphA2 overexpression resulted in significantly increased tumor growth and microvessel density, suggesting that increased angiogenesis likely contributed to the greater tumor growth.…”

“…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. Indeed, these approaches demonstrated decreased tumor growth and improved survival in orthotopic ovarian cancer mouse models.…”

Focal adhesion kinase

“…41 Tumor MVD was calculated as the average CD31-positive vessel count over 5 sections under x200 high-power fields (HPF). A vessel was defined as an open lumen with 1 or more immediately adjacent CD31-positive cell(s).…”