ArticleLaboratory investigation; a journal of technical methods and pathology2010
Molecular blockade of VEGFR2 in human epithelial ovarian carcinoma cells.
Article in Laboratory investigation; a journal of technical methods and pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Dihydroartemisinin inhibits metastatic potential and cancer stemness by modulating the miR-200b-BMI-1/VEGF-A axis in ovarian cancer.Experimental & molecular medicine · 2025Article
- Physicochemical and biological characterization of a bispecific antibody in a CrossMab/KIH format that targets EGFR and VEGF-A.Frontiers in immunology · 2025Article
- Novel NO-TZDs and trimethoxychalcone-based DHPMs: design, synthesis, and biological evaluation as potential VEGFR-2 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- VGLL3 expression is associated with macrophage infiltration and predicts poor prognosis in epithelial ovarian cancer.Frontiers in oncology · 2023Article
- Design, Synthesis, and Biological Evaluation of a Novel VEGFR-2 Inhibitor Based on a 1,2,5-Oxadiazole-2-Oxide Scaffold with MAPK Signaling Pathway Inhibition.Pharmaceuticals (Basel, Switzerland) · 2022Article
- AAV8-mediated sVEGFR2 and sVEGFR3 gene therapy combined with chemotherapy reduces the growth and microvasculature of human ovarian cancer and prolongs the survival in mice.Frontiers in medicine · 2022Article
- Dioscin suppresses the viability of ovarian cancer cells by regulating the VEGFR2 and PI3K/AKT/MAPK signaling pathways.Oncology letters · 2018Article
- A computational framework for complex disease stratification from multiple large-scale datasets.BMC systems biology · 2018Article
- Pilot assessment of vascular endothelial growth factor receptors and trafficking pathways in recurrent and metastatic canine subcutaneous mast cell tumours.Veterinary medicine and science · 2017Article
- Role of NRP-1 in VEGF-VEGFR2-Independent Tumorigenesis.Targeted oncology · 2016Review
- The relationship of the angiogenesis regulators VEGF-A, VEGF-R1 and VEGF-R2 to p53 status and prognostic factors in epithelial ovarian carcinoma in FIGO-stages I-II.International journal of oncology · 2016Article
- VEGFR2 inhibition by RNA interference affects cell proliferation, migration, invasion, and response to radiation in Calu-1 cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Article
- Solamargine triggers cellular necrosis selectively in different types of human melanoma cancer cells through extrinsic lysosomal mitochondrial death pathway.Cancer cell international · 2016Article
- sMEK1 inhibits endothelial cell proliferation by attenuating VEGFR-2-dependent-Akt/eNOS/HIF-1α signaling pathways.Oncotarget · 2015Article
- Vascular endothelial growth factor directly stimulates tumour cell proliferation in non-small cell lung cancer.International journal of oncology · 2015Article
- Anti-Angiogenic Drugs: Involvement in Cutaneous Side Effects and Wound-Healing Complication.Advances in wound care · 2014Review
- Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype.EMBO molecular medicine · 2014Article
- Modeling of hypo/hyperglycemia and their impact on breast cancer progression related molecules.PloS one · 2014Article
- VEGF targets the tumour cell.Nature reviews. Cancer · 2013Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Human epithelial ovarian cancer (EOC) is the most lethal neoplasm affecting the female genital tract, and is characterized by overexpression of vascular endothelial growth factor (VEGF) and growth as ascites. Anti-VEGF strategies are currently used in EOC therapy with promising results; however, molecular targeting of specific VEGF receptors on the cancer cells themselves has not been explored to date. We previously showed that activation of a VEGF/VEGFR2 signaling loop in EOC cells supports their survival in suspension, and short-term pharmacological inhibition of this loop increased EOC cell apoptosis in vitro. In this study, we stably knocked down VEGFR2 in OVCAR-3 and SKOV-3 EOC cells using short hairpin RNA (shRNA), an RNA interference strategy that could potentially overcome chemoresistance arising with angiogenic inhibitors. Unexpectedly, we observed an induction of more aggressive cellular behavior in transfected cells, leading to increased growth in mouse xenografts, enhanced accumulation of ascites, increased VEGF and neuropilin-1 (NRP-1) expression, and decreased expression of adhesion proteins, notably cadherins and integrins. Sonic hedgehog (SHH) pathways do not seem to be involved in the upregulation of NRP-1 message in VEGFR2 knockdown cells. Supporting our mouse model, we also found a significant increase in the ratio between NRP-1 and VEGFR2 with increasing tumor grade in 80 cases of human EOC. The change in EOC behavior that we report in this study occurred independent of the angiogenic response and shows the direct effect of VEGF blockade on the cancer cells themselves. Our findings highlight the possible confounding events that may affect the usefulness of RNAi in a therapeutic setting for disrupting EOC cell survival in ascites.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.