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

• Published in: Hypoxia Vol. 5; pp. 1 - 9
• Main Authors: Seeley, Todd W, Sternlicht, Mark D, Klaus, Stephen J, Neff, Thomas B, Liu, David Y
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2017; Dove Medical Press
• Subjects: Age; Amino acids; Anemia; Angiogenesis; Breast cancer; Clinical trials; Endoplasmic reticulum; Females; Gene expression; Hypoxia; Kidney diseases; Kinases; Laboratory animals; Metastasis; Mutation; Original Research; Proteins; Studies; Tumors; Vascular endothelial growth factor; Canada; United States > US; hypoxia-inducible factor; erythropoiesis; cancer progression; hypoxia-inducible factor prolyl hydroxylase inhibitors; MMTV-Neu breast cancer model; vascular endothelial growth factor
• ISSN: 2324-1128; 2324-1128
• DOI: 10.2147/hp.s130526

The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neu -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.