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Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neu(ndl)-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-...

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Autores principales: Seeley, Todd W, Sternlicht, Mark D, Klaus, Stephen J, Neff, Thomas B, Liu, David Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354531/
https://www.ncbi.nlm.nih.gov/pubmed/28331872
http://dx.doi.org/10.2147/HP.S130526
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author Seeley, Todd W
Sternlicht, Mark D
Klaus, Stephen J
Neff, Thomas B
Liu, David Y
author_facet Seeley, Todd W
Sternlicht, Mark D
Klaus, Stephen J
Neff, Thomas B
Liu, David Y
author_sort Seeley, Todd W
collection PubMed
description The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neu(ndl)-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592). In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors.
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spelling pubmed-53545312017-03-22 Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer Seeley, Todd W Sternlicht, Mark D Klaus, Stephen J Neff, Thomas B Liu, David Y Hypoxia (Auckl) Original Research The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neu(ndl)-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592). In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. Dove Medical Press 2017-03-10 /pmc/articles/PMC5354531/ /pubmed/28331872 http://dx.doi.org/10.2147/HP.S130526 Text en © 2017 Seeley et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Seeley, Todd W
Sternlicht, Mark D
Klaus, Stephen J
Neff, Thomas B
Liu, David Y
Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer
title Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer
title_full Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer
title_fullStr Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer
title_full_unstemmed Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer
title_short Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer
title_sort induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a vegf-sensitive model of spontaneous breast cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354531/
https://www.ncbi.nlm.nih.gov/pubmed/28331872
http://dx.doi.org/10.2147/HP.S130526
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