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Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma
PURPOSE: Expression of the hypoxia-inducible factor (HIF)-1-regulated gene product, vascular endothelial growth factor (VEGF), correlates with tumor vascularity in patients with uveal melanoma (UM). While the relationship between HIF-1 and VEGF in cancer is well-studied, their relative contribution...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884956/ https://www.ncbi.nlm.nih.gov/pubmed/26761211 http://dx.doi.org/10.18632/oncotarget.6868 |
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author | Hu, Ke Babapoor-Farrokhran, Savalan Rodrigues, Murilo Deshpande, Monika Puchner, Brooks Kashiwabuchi, Fabiana Hassan, Syed Junaid Asnaghi, Laura Handa, James T. Merbs, Shannath Eberhart, Charles G. Semenza, Gregg L. Montaner, Silvia Sodhi, Akrit |
author_facet | Hu, Ke Babapoor-Farrokhran, Savalan Rodrigues, Murilo Deshpande, Monika Puchner, Brooks Kashiwabuchi, Fabiana Hassan, Syed Junaid Asnaghi, Laura Handa, James T. Merbs, Shannath Eberhart, Charles G. Semenza, Gregg L. Montaner, Silvia Sodhi, Akrit |
author_sort | Hu, Ke |
collection | PubMed |
description | PURPOSE: Expression of the hypoxia-inducible factor (HIF)-1-regulated gene product, vascular endothelial growth factor (VEGF), correlates with tumor vascularity in patients with uveal melanoma (UM). While the relationship between HIF-1 and VEGF in cancer is well-studied, their relative contribution to the angiogenic phenotype in UM has not previously been interrogated. Here we evaluate the contribution of HIF-1, VEGF, and a second HIF-1-regulated gene product, angiopoietin-like 4 (ANGPTL4), to angiogenesis in UM. EXPERIMENTAL DESIGN: UM cells were examined for expression of HIF-1α, VEGF, and ANGPTL4. Their contribution to the angiogenic potential of UM cells was assessed using the endothelial cell tubule formation and directed in vivo angiogenesis assays. These results were corroborated in tissue from UM animal models and in tissue from patients with UM. RESULTS: Inhibition of VEGF partially reduced tubule formation promoted by conditioned medium from UM cells. Inhibition of ANGPTL4, which was highly expressed in hypoxic UM cells, a UM orthotopic transplant model, a UM tumor array, and vitreous samples from UM patients, inhibited the angiogenic potential of UM cells in vitro and in vivo; this effect was additive to VEGF inhibition. CONCLUSIONS: Targeting both ANGPTL4 and VEGF may be required for the effective inhibition of angiogenesis in UM. |
format | Online Article Text |
id | pubmed-4884956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48849562016-06-17 Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma Hu, Ke Babapoor-Farrokhran, Savalan Rodrigues, Murilo Deshpande, Monika Puchner, Brooks Kashiwabuchi, Fabiana Hassan, Syed Junaid Asnaghi, Laura Handa, James T. Merbs, Shannath Eberhart, Charles G. Semenza, Gregg L. Montaner, Silvia Sodhi, Akrit Oncotarget Research Paper PURPOSE: Expression of the hypoxia-inducible factor (HIF)-1-regulated gene product, vascular endothelial growth factor (VEGF), correlates with tumor vascularity in patients with uveal melanoma (UM). While the relationship between HIF-1 and VEGF in cancer is well-studied, their relative contribution to the angiogenic phenotype in UM has not previously been interrogated. Here we evaluate the contribution of HIF-1, VEGF, and a second HIF-1-regulated gene product, angiopoietin-like 4 (ANGPTL4), to angiogenesis in UM. EXPERIMENTAL DESIGN: UM cells were examined for expression of HIF-1α, VEGF, and ANGPTL4. Their contribution to the angiogenic potential of UM cells was assessed using the endothelial cell tubule formation and directed in vivo angiogenesis assays. These results were corroborated in tissue from UM animal models and in tissue from patients with UM. RESULTS: Inhibition of VEGF partially reduced tubule formation promoted by conditioned medium from UM cells. Inhibition of ANGPTL4, which was highly expressed in hypoxic UM cells, a UM orthotopic transplant model, a UM tumor array, and vitreous samples from UM patients, inhibited the angiogenic potential of UM cells in vitro and in vivo; this effect was additive to VEGF inhibition. CONCLUSIONS: Targeting both ANGPTL4 and VEGF may be required for the effective inhibition of angiogenesis in UM. Impact Journals LLC 2016-01-09 /pmc/articles/PMC4884956/ /pubmed/26761211 http://dx.doi.org/10.18632/oncotarget.6868 Text en Copyright: © 2016 Hu et al. https://creativecommons.org/licenses/by/2.5/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Hu, Ke Babapoor-Farrokhran, Savalan Rodrigues, Murilo Deshpande, Monika Puchner, Brooks Kashiwabuchi, Fabiana Hassan, Syed Junaid Asnaghi, Laura Handa, James T. Merbs, Shannath Eberhart, Charles G. Semenza, Gregg L. Montaner, Silvia Sodhi, Akrit Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma |
title | Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma |
title_full | Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma |
title_fullStr | Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma |
title_full_unstemmed | Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma |
title_short | Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma |
title_sort | hypoxia-inducible factor 1 upregulation of both vegf and angptl4 is required to promote the angiogenic phenotype in uveal melanoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884956/ https://www.ncbi.nlm.nih.gov/pubmed/26761211 http://dx.doi.org/10.18632/oncotarget.6868 |
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