Efficacy and Antivascular Effects of EphA2 Reduction With an Agonistic Antibody in Ovarian Cancer

Landen, Charles N.; Lü, Chunhua; Han, Liz Y.; Coffman, Karen; Bruckheimer, Elizabeth; Halder, Jyotsnabaran; Mangala, Lingegowda S.; Merritt, William M.; Lin, Yvonne G.; Gao, Changhou; Schmandt, Rosemarie; Kamat, Aparna A.; Li, Yang; Thaker, Premal H.; Gershenson, David M.; Parikh, Nila U.; Gallick, Gary E.; Kinch, Michael S.; Sood, Anil K.

doi:10.1093/jnci/djj414

Cited by 125 publications

(147 citation statements)

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“…The effect of EphA2 transfection into poorly-aggressive ovarian cancer cells with regard to metastatic ability was determined by using an orthotopic nude mouse model of ovarian carcinoma, which was previously described. 7,17,32 Two clones of A2780-EphA2 cells, the non-transfected and vector-alone transfected A2780-neo cells were injected i.p. into female nude mice.…”

Section: Epha2 Overexpression Promotes Cell-ecm Attachmentmentioning

confidence: 99%

“…Based on our previous work related to reduced angiogenesis with EphA2 silencing, 7,33 we next asked whether the increased tumor growth with A2780-EphA2 cells was related to increased angiogenesis. To investigate this possibility, we examined microvessel density.…”

Section: Epha2 Overexpression Promotes Cell-ecm Attachmentmentioning

confidence: 99%

“…For example, reducing EphA2 level using an agonist antibody or siRNA approaches can effectively decrease tumor growth in orthotopic ovarian cancer mouse models. 7,33 The antitumor efficacy was reflective of anti-angiogenic effects mediated, in part, by reduced levels of vascular endothelial growth factor (VEGF) levels. 7 Similar results with regard to the growth inhibitory effects of EphA2 suppression have been demonstrated in breast and prostate cancers, glioma and malignant mesothelioma.…”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

“…1,5,6 For oncology applications, interest in EphA2 has grown recently due to its increased expression in most cancers including lung, breast, ovary, prostate, colorectal, skin and esophagus. [7][8][9][10][11][12][13] Interestingly, EphA2 is located on chromosome 1p36.1, which is a hotspot for rearrangements in many human cancers including ovarian cancer. [14][15][16] We have previously demonstrated that EphA2 is overexpressed in 76% of epithelial ovarian cancers.…”

Section: Introductionmentioning

confidence: 99%

“…7,19 The mechanisms underlying this therapeutic efficacy were related to reduced levels of VEGF following decreased EphA2 levels and tumor angiogenesis. 7,19 While these data have provided an increasing understanding of the role that EphA2 plays in malignant tumor behavior, in the current study, we asked whether increased EphA2 expression in poorly invasive ovarian cancer cells could directly promote malignant behavior. To answer this question, we utilized a series of in vitro and in vivo experiments following introduction of EphA2 into a non-expressing cell line.…”

Section: Introductionmentioning

confidence: 99%

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EphA2 overexpression promotes ovarian cancer growth

Lü

Shahzad

Wang

et al. 2008

Cancer Biology & Therapy

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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.

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Section: Epha2 Overexpression Promotes Cell-ecm Attachmentmentioning

confidence: 99%

Section: Epha2 Overexpression Promotes Cell-ecm Attachmentmentioning

confidence: 99%

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EphA2 overexpression promotes ovarian cancer growth

Lü

Shahzad

Wang

et al. 2008

Cancer Biology & Therapy

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Oncogenic gene TRIM10 confers resistance to cisplatin in osteosarcoma cells and activates the NF‐κB signaling pathway

Bao

Zhou

et al. 2020

Cell Biology International

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Deregulation of tripartite motif (TRIM) family proteins contribute to multiple biological processes such as neurodegeneration, development, inflammation, cell survival, apoptosis, and carcinogenesis. However, the biological function and molecular mechanism of TRIM family proteins in osteosarcoma chemoresistance remain unclear. In the current study, we found the protein expression of TRIM10 was markedly overexpressed in cisplatin resistance's osteosarcoma tissues and TRIM10 overexpression was inversely correlated with osteosarcoma patient survival. Furthermore, overexpression of TRIM10 confers cisplatin resistance on osteosarcoma cells; however, repressing TRIM10 sensitized osteosarcoma cell lines to cisplatin cytotoxicity in vitro. Mechanically, TRIM10 upregulated the nuclear levels of p65, thereby activating canonical NF‐κB signaling. Taken together, our results suggest that TRIM10 contributed to cisplatin resistance in osteosarcoma cells, and targeting the TRIM10/p65 axis may represent a promising strategy to enhance cisplatin response in osteosarcoma patients with chemoresistance.

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EphA2 overexpression is associated with angiogenesis in ovarian cancer

Lin

Han

Kamat

et al. 2007

Cancer

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103

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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.

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Efficacy and Antivascular Effects of EphA2 Reduction With an Agonistic Antibody in Ovarian Cancer

Abstract: EA5 in combination with paclitaxel decreased tumor growth in an orthotopic ovarian cancer mouse model through antiangiogenic mechanisms associated with reduced levels of VEGF and phosphorylated Src. Humanized antibody constructs against EphA2 are worthy of future study.

Cited by 125 publications

References 53 publications

EphA2 overexpression promotes ovarian cancer growth

EphA2 overexpression promotes ovarian cancer growth

Oncogenic gene TRIM10 confers resistance to cisplatin in osteosarcoma cells and activates the NF‐κB signaling pathway

EphA2 overexpression is associated with angiogenesis in ovarian cancer

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